The Certihaler is a new multi-dose dry powder inhaler for the delivery of formoterol (Foradil), a long-acting beta(2)-agonist. This dose-ranging study compared the efficacy and safety of formoterol 5, 10, 15 and 30 microg and placebo administered via the Certihaler or formoterol 12 microg via a single-dose dry powder inhaler (Aerolizer) in children with persistent asthma. This was a randomized, placebo-controlled, double-blind, double-dummy, incomplete block crossover, dose-finding and pharmacokinetic study. Children (5-12 years, n = 77) received four of the active treatments twice weekly (BID) for 1 week separated by 1-week single-blind washouts. The primary efficacy variable was 12-h AUC of FEV(1) after 1 week's treatment. Secondary variables included serial 12-h FEV(1). A subset of patients (n = 37) participated in a pharmacokinetic analysis. All formoterol doses resulted in significant increases in 12-h AUC of FEV(1) compared with placebo, and there was no difference between active treatments. The onset of action of formoterol was <3 min for all active treatments. Doses of formoterol > or =10 microg via the Certihaler increased FEV(1) significantly for up to 12 h compared with placebo. The 5 microcg dose via the Certihaler and 12 microg dose via the Aerolizer had a significant effect up to 8 and 7 h post-dose, respectively. Urinary excretion of formoterol via the Certihaler increased in a dose-proportional manner. All formoterol doses were well tolerated, but some patients experienced tremor at the 15 and 30 microg doses. Despite the lack of significant differences between the active doses in the overall bronchodilation, formoterol 10 microg BID via the Certihaler was the dose that provided the best balance between efficacy and tolerability: its duration of action was sustained over 12 h, contrary to that the lower dose (5 microg BID), whereas its tolerability, especially with regard to tremor, was better than the higher doses (15 and 30 microg BID). Overall, Certihaler 10 microg BID was not significantly different from formoterol 12 microg BID via Aerolizer.

Evaluation of patients with chronic obstructive pulmonary disease (COPD) often includes the use of post-bronchodilator reversibility testing to guide treatment decisions. Recommendations for reversibility testing differ and there is no universally accepted method or outcome criterion. A survey of recent clinical trials with beta2-agonists in COPD illustrates the diversity of methods used to assess reversibility and highlights the difficulty of comparing data from such trials. Two recent studies demonstrated the benefits of treatment with the long-acting beta2-agonist bronchodilator formoterol (Foradil Aerolizer) in patients with COPD. When patients were classified according to their degree of reversibility as partially or poorly reversible, improvements were observed in both groups irrespective of the definition applied. These results suggest that bronchodilator reversibility testing should not be used as a rigid basis for treatment decisions with beta2-agonists in COPD patients. There is a pressing need for the role of reversibility testing to be clearly defined.

Background: For maximum treatment compliance there is a need to provide asthma patients with devices that suit their particular preferences. The Foradil® Certihaler™ is a novel multi-dose dry powder inhaler developed to increase the choice of devices available. Objectives: To evaluate the safety and efficacy of formoterol administered via the Foradil Certihaler, or via the single-dose inhaler Foradil® Aerolizer®. Methods: This was a randomized, placebo-controlled, double-dummy, incomplete block crossover, dose-ranging and pharmacokinetic study in patients with persistent asthma. Sixty-seven patients (mean 48.0 years) were randomized to formoterol 5, 10, 15 and 30 µg twice daily via the Certihaler, 12 µg formoterol b.i.d. via the Aerolizer, or placebo in four 1-week double-blind treatment periods separated by 1-week single-blind washouts. Results: All formoterol doses delivered via the Certihaler or the Aerolizer significantly increased FEV1 compared with placebo (p < 0.0001). Formoterol demonstrated an onset of action of <3 min. All active treatments were well tolerated. Tremor was the most common adverse event and was more pronounced at high doses. At lower doses the incidence of tremor with the Certihaler was similar to that observed with placebo or the Aerolizer. The pharmacokinetic evaluation comprised 41 patients (mean 45.9 years). Urinary excretion of unchanged formoterol and total formoterol increased with dose delivered via the Certihaler. The optimum dose of formoterol via the Certihaler was 10 µg. Conclusion: Delivery of formoterol via the Certihaler or Aerolizer combines rapid relief with enduring control and provides convenient bronchodilation in patients with persistent asthma.

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 1 s (FEV1) of <12% from the patient's predicted normal value after salbutamol inhalation were included. Patients inhaled single doses of formoterol (12 and 24 ng), 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 4 h 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.

Objective: To assess the peak inspiratory flow rate (PIFR) and forced inspiratory vital capacity (FIVC) through the formoterol (Foradil*) Aerolizer* in patients with mild, moderate and severe asthma.Research design and methods: PIFR and FIVC were assessed in 33 adults and 32 children using a spirometer alone (baseline), a spirometer with an adaptor, and a spirometer with an adaptor and the Aerolizer inhaler (placebo loaded).Results: Of adult patients using the Aerolizer inhaler, 73% had PIFR values of > 100 l/min and 91% had values of > 60 l/min. PIFR in adults was reduced from a mean baseline of 283 l/min to 118 l/min through the loaded Aerolizer inhaler Similarly, 75% of children using the Aerolizer inhaler had PIFR values > 80 l/min and 91% had values of > 60 l/min. The mean PIFR in children was reduced from a baseline of 154 l/min to 100 l/min through the loaded Aerolizer inhaler. Only small mean decreases from baseline were observed in FIVC through the loaded Aerolizer inhaler: 8.4% in adults and 3.8% in children. FIVC values of > 2.0 litre were achieved in 82% of adults, and 81% of children achieved FIVC values of > 1.5 litre.Conclusion: This study, albeit in a relatively small patient population, suggests that most children and adults with asthma can generate PIFRs of > 60 l/min and FIVCs of > 1.5 litre through the Aerolizer inhaler regardless of their disease severity. Such findings compare extremely favourably with other dry powder inhalers.

RESUMO: As normas internacionais para o tratamento da asma brônquica recomendam que os doentes com sintomatologia mal controlada com doses baixas/ /intermédias de corticosteróides (CT) inalados sejam submetidos a doses mais elevadas de CT e, se necessário, deverá ser adicionado um β2 agonista de longa duração. No entanto, estudos mais recentes demonstraram que a adição deste fármaco a doses baixas/moderadas de CT inalados permite um melhor controlo da sintomatologia do que a duplicação da dose de CT. O formoterol constitui o β2 agonista de eleição devido ao seu início de acção rápida.O objectivo do presente trabalho foi comparar a eficácia da associação do β2 agonista formoterol a doses médias/elevadas de CT inalados com a duplicação da dose do CT em indivíduos com asma moderada/grave mal controlada.Foram avaliados doentes com idade superior a 18 anos com asma moderada e grave que apresentavam um FEV1≥50% do previsto e um aumento≥15% do referido parâmetro após inalação de um broncodilatador de curta duração, tendo sido submetido a terapêutica com CT inalados diariamente (dipropionato de beclometasona 1000 μ - budesonida 800 μg) no mês que precedeu o início do estudo em análise. A existência de, pelo menos, dois dos parâmetros seguintes, nos últimos 7 dias do período de run-in, foi imprescindível: sintomatologia interferindo com as actividades de vida diária; interrupção do sono por sintomas nocturnos, necessidade de terapêutica de alívio numa dose≥4 puffs salbutamol/dia; variabilidade diária do PEF (Peak Expiratory Flow)≥15%.Foram critérios de exclusão: doentes cuja dose do CT inalado diária foi alterada no último mês; indivíduos submetidos a CT oral ou β2 agonista de longa duração no mês precedente; doentes com dificuldade de utilizar o aerolizer apesar da instrução adequada.Tratou-se de um estudo randomizado, duplamente cego, envolvendo 203 indivíduos: 102 submetidos a formoterol 12 μg e dipropionato de beclometasona 500 μg duas vezes/dia; 101 sob este corticosteróide na dose de 1000 μg duas vezes/dia e placebo. Ambos os grupos foram tratados com os referidos fármacos durante 12 semanas. Os doentes estudados apresentavam um FEV1 72% do previsto, uma reversibilidade desencadeada pelo (β2 agonista de curta duração de 27%, scores de sintomas moderados e necessidade de terapêutica de alívio na dose≥5 puffs de salbutamol/ dia.A diferença do PEF entre os dois grupos foi de 27,78 1/minuto, sendo favorável à associação formoterol/beclometasona (p=0,0002). Foi observada, também, uma diferença estatisticamente significativa na relação cortisol/ creatinina urinário após o tratamento de 12 semanas (p=0,001), indicando supressão do eixo hipotalâmico-hipofisário nos doentes sob 1000 μg de dipropionato de beclometasona duas vezes/ dia. Os scores de sintomas foram significativamente mais baixos nos doentes sob terapêutica combinada, sendo a proporção de doentes livres de sintomas durante o dia duas vezes superior neste grupo e a utilização de terapêutica de alívio inferior. COMENTÁRIO: Este estudo demonstra que, no tratamento de doentes com asma moderada/grave não controlada com dipropionato de beclometasona 1000 μg/dia, a adição de formoterol 12 μg duas vezes/dia é mais eficaz do que a duplicação da dose de beclometasona.A terapêutica combinada melhora significativamente os parâmetros objectivos da obstrução das vias aéreas quando comparada com altas doses de corticosteróides inalados. O efeito benéfico de adição de formoterol na função pulmonar tornou-se evidente após quatro semanas de tratamento e permaneceu inalterada até ao fim do estudo. Este efeito pode dever-se ao antagonismo funcional do formoterol à contracção do músculo liso, à sua capacidade de estabilizar os mastócitos ou de reduzir o edema da parede brônquica.As exacerbações ligeiras e moderadas ocorreram com maior frequência no grupo sob altas doses de CT inalados. Estes resultados foram sobreponíveis aos observados anteriormente em doentes com asma ligeira submetidos à associação formoterol/budesonido (dose baixa/intermédia) ou a doses elevadas deste último fármaco. Também neste estudo se verificou um maior número de exacerbações no segundo grupo.Elevadas doses de CT inalados estão relacionadas com significativos efeitos suprarrenais. Assim, a associação de um β2 agonista de longa acção (formoterol) permite o controlo da doença sem necessidade de doses altas de CT inalados. Neste estudo, o quociente cortisol/creatinina urinário foi significativamente menor no grupo sob corticoterapia em dose elevada do que nos indivíduos submetidos a terapêutica combinada, traduzindo uma maior supressão do risco hipotalâmico-hipofisário no primeiro caso. Estes achados vieram confirmar a observação de que o dipropionato de beclometasona na dose≥1500 μg/dia exerce um efeito supressor significativo na libertação de cortisol endógeno.A terapêutica combinada de CT inalados e β2 agonistas de longa acção permitiu um bom controlo da asma brônquica, comparativamente a baixas doses de CT, e conduziu à administração dos fármacos inalados em doses fixas através de um dispositivo único. Ringdal e colaboradores compa-raram a eficácia do salmeterol 50 μg/ fluticasona 250 μg utilizando Diskus duas vezes/dia com o formoterol 12 μg/ budesonido 500 μg administrados separadamente através do Turbohaler duas vezes/ /dia. A primeira associação foi significativamente superior na redução das exacerbações de asma e dos sintomas nocturnos, apesar da dose mais baixa de fluticasona comparada com a de budesonido. Estes resultados não são, no entanto, inesperados, visto a fluticasona ser mais potente do que o budesonido.Apesar de a administração de fármacos em doses fixas num único dispositivo ter vantagens adicionais em termos de aderência ao tratamento e conveniência, não apresenta grande flexibilidade no ajuste da dose durante as exacerbações. São, assim, necessários novos estudos para avaliar os dispositivos mais apropriados, de forma a obter o maior sinergismo de acção entre β2 agonista de longa duração e os CT inalados. Palavras-chave: Asma moderada/grave, β2 agonista de longa acção, formoterol, corticosteróides inalados, beclometasona

RATIONALE: Symptoms of seasonal allergic rhinitis (SAR) are determined by patients' individual sensitivity and exposure to relevant allergens.This analysis evaluated the relationship of pollen levels to the treatment effect of montelukast for symptoms of SAR.METHODS: Multicenter, randomized, double-blind, parallel-group studies were conducted during 3 consecutive tall allergy seasons.Symptomatic patients age >_15 years were randomly assigned monteluka~st 10-mg (n=929) or placebo (n=933) once-daily for 2 weeks and recorded symptoms daily on diary cards.For analysis, patients were divided into subgroups based on their weed pollen exposure (average of daily pollen counts over their 2week treatment period); subgroups were also defined by the timing of the 2week treatment period relative to the peak of the weed pollen season.RESULTS: Montelukast significantly improved the daytime nasal symptoms score (p<0.001) compared with placebo.Montelukast treatment effect was significantly greater in patients exposed to higher weed pollen levels (> 10 grains/m3/24-hr) compared with patients exposed to lower levels (p<0.05).Data also suggested that treatment effect was lowest (as the placebo improvement increased) in patients exposed to low pollen levels after the peak of the pollen season.CONCLUSIONS: Montelukast significantly improved daytime nasal symptoms during fall allergy seasons and this effect was most marked in patients exposed to higher pollen levels.

This double-blind. randomised, multi-centre, parallel-group study compared the effect of adding Foradil(R) (formoterol fumarate) to existing medium-high doses of inhaled corticosteroids (ICS) with that of doubling the dose of ICS in patients with sub-optimally controlled asthma.After a run-in period, 203 patients with moderate-to-severe asthma who remained symptomatic despite treatment with 500 mug beclomethasone twice daily, were randomised to receive either 12 mug formoterol twice daily (Foradil(R) Aerolizer(R) Novartis) in addition to beclomethasone 500 mug twice daily, or beclomethasone 1000 mug twice daily and placebo for 12 weeks. The primary efficacy variable was mean morning pre-medication peak expiratory flow (PEF) during the last seven days of treatment.The difference in PEF between treatments was 27.78 l/min in favour of the formoterol/beclomethasone combination (95% CI 13.42, 42.14 l/min, p = 0.0002, intention-to-treat population). Significant differences in the urinary cortisol/creatinine ratio between treatment groups at 12 weeks (p = 0.001) indicated suppression of the hypothalamic-pituitary-adrenal axis in the patients on beclomethasone 1000 mug twice daily.The addition of formoterol 12 mug twice daily to beclomethasone in patients with asthma who were poorly controlled with beclomethasone 500 mug twice daily was more effective than doubling the ICS dose and resulted in less suppression of the hypothalamic-pituitary-adrenal axis. (C) 2003 Elsevier Ltd. All rights reserved.

As normas internacionais para o tratamento da asma brônquica recomendam que os doentes com sintomatologia mal controlada com doses baixas/ /intermédias de corticosteróides (CT) inalados sejam submetidos a doses mais elevadas de CT e, se necessário, deverá ser adicionado um β2 agonista de longa duração. No entanto, estudos mais recentes demonstraram que a adição deste fármaco a doses baixas/moderadas de CT inalados permite um melhor controlo da sintomatologia do que a duplicação da dose de CT. O formoterol constitui o β2 agonista de eleição devido ao seu início de acção rápida.

STUDY OBJECTIVE:To compare the efficacy, tolerability, and safety of therapy with formoterol and oral slow-release theophylline (THEO) in patients with COPD. DESIGN:A randomized, parallel-group study, with double-blind arms for formoterol and placebo (PL) and an open arm for oral slow-release THEO administered in individual doses on the basis of plasma concentrations. SETTING:Eighty-one centers worldwide. PATIENTS:Eight hundred fifty-four patients with symptomatic COPD. INTERVENTION:Comparison of twice-daily inhaled formoterol dry powder (12 or 24 microg), PL, and THEO (individualized doses) over 12 months. MEASUREMENTS AND RESULTS:Compared to PL, doses of formoterol and THEO both significantly improved the area under the curve for FEV(1) measured over a period of 12 h following the morning dose of study medication at 3 and 12 months (p < 0.001 for all comparisons). Therapy with formoterol, 12 microg, was significantly more effective than that with THEO (p < or = 0.026). Formoterol significantly reduced the percentage of "bad days" (i.e., days with at least two individual symptom scores > or = 2 and/or a reduction in peak expiratory flow from a baseline of > 20%; p < or = 0.035 vs. PL and THEO), and the use of salbutamol rescue medication (p < or = 0.003 vs PL) over the whole treatment period, while the effect of THEO was similar to that of PL. Therapy with formoterol and THEO was more effective than PL at improving quality of life for > 12 months (p < or = 0.030). Treatment-related adverse events and discontinuations were more frequent among patients receiving THEO than among those receiving formoterol. CONCLUSIONS:Long-term treatment with inhaled formoterol dry powder is more effective and better tolerated than treatment with therapeutically appropriate doses of oral slow-release THEO in symptomatic patients with COPD.

Over 500 children with asthma, aged 5-12 years, have been treated with formoterol fumarate (Foradil) delivered via the Aerolizer dry powder inhaler in clinical trials, with treatment periods of up to 15 months. In pivotal double-blind trials, two dose levels, 12 and 24 microg taken twice daily, provided significant benefit in terms of lung function measurements and symptom control (a lower dose of 6 microg twice daily appeared insufficient with this formulation). The higher, 24 microg dose appeared to provide an additional margin of benefit in a subgroup of children with more unstable/severe disease when the results from long-term follow-up (12-15 months) were analysed. Formoterol was shown to have a good safety profile when taken as regular maintenance treatment and when used as rescue medication by patients already receiving formoterol as regular maintenance treatment. In this flexible regimen, with formoterol used for rescue and maintenance, the overall daily intake of formoterol was low, with 96.1% of all treatment days (n = 2452) covered by a total daily dose (regular + rescue) of 48 microg (four doses) or less. There was no increase in the average daily intake of rescue formoterol over time. The clinical efficacy associated with this regimen was maintained over time and, in the case of morning peak expiratory flow rate, steadily improved over time. The Foradil Aerolizer inhalation system is simple to use and has a low resistance to inspiratory airflow that maximises the patient's control over dosing, while minimising the risk of under- and overdosing. These features may be especially valuable in a young patient population.

Background: Inhaled short-acting beta(2)-adrenoceptor agonists are the most commonly used treatment for the prevention of exercise-induced bronchoconstriction (EIB). Formoterol, a long-acting beta2-adrenoceptor agonist, has been demonstrated to provide protection from EIB, although the onset and duration of this protection have not been defined.Objective: The purpose of this study was to determine the onset and duration of the protective effect of a single dose of inhaled formoterol powder against EIB, comparing them with the effect of a single dose of placebo and albuterol administered via metered-dose inhaler (MDI).Methods: In this double-dummy, 4-way crossover study, patients received single doses of formoterol (12 and 24 mug) via a powder inhaler, albuterol by MDI (180 mug), and placebo. Exercise challenge tests (ECTs) were conducted at 15 minutes and at 4, 8, and 12 hours postdose. Pulmonary function studies (forced expiratory volume in I second [FEV1] and peak expiratory flow rate) were performed before and after each exercise challenge.Results: Twenty adolescent and adult patients (mean age, 23.8 years; range, 13-41 years; 9 male, I I female) with asthma were enrolled in the study, and 17 completed all 4 treatment sequences. Compared with placebo, both doses of formoterol produced significantly greater inhibition of FEV1 decreases at all time points (P < 0.01). There were no significant differences in efficacy measures between the 2 formoterol doses throughout the study. The exercise-induced decrease in FEV1 after albuterol treatment was significantly reduced compared with placebo only at 15 minutes after dosing (P < 0.05). Formoterol and albuterol exhibited a similar rapid onset of action (<15 minutes), but formoterol continued to protect patients against EIB for at least 12 hours (P < 0.01), whereas albuterol was no longer clinically effective by the 4-hour ECT.Conclusions: Formoterol and albuterol, given as single-dose inhalations, both provided protection from EIB within 15 minutes in this group of patients. The bronchoprotection afforded by formoterol lasted up to 12 hours, whereas that of albuterol was no longer significant by 4 hours.

Numerous clinical trials have investigated the use of formoterol, a long‐acting β2–agonist, for the treatment of chronic obstructive pulmonary disease (COPD). Formoterol provides bronchodilation as rapidly as albuterol, yet its efficacy and duration of action are similar to those of salmeterol. It demonstrates better spirometric efficacy than either ipratropium or theophylline alone, and its efficacy improves when administered in combination with ipratropium. Formoterol improves patients' quality of life and has a good safety profile. It is better tolerated than theophylline and has a similar tolerability to albuterol, salmeterol, and ipratropium. In short, formoterol is a bronchodilator with rapid onset of action and prolonged duration of action with a favorable efficacy, safety, and tolerability profile when used in patients with COPD. It provides a valid therapeutic option in the pharmacologic treatment of this disease.

Summary Over 500 children with asthma, aged 5-12 years, have been treated with formoterol fumarate (Foradilt) delivered via the Aerolizer dry powder inhaler in clinical trials, with treatment periods of up to 15 months. In pivotal double-blind trials, two dose levels, 12 and 24 |ig taken twice daily, provided significant benefit in terms of lung function measurements and symptom control (a lower dose of 6 |ig twice daily appeared insufficient with this formulation). The higher, 24 |ig dose appeared to provide an additional margin of benefit in a subgroup of children with more unstable/severe disease when the results from long-term follow-up (12-15 months) were analysed. Formoterol was shown to have a good safety profile when taken as regular maintenance treatment and when used as rescue medication by patients already receiving formoterol as regular maintenance treatment. In this flexible regimen, with formoterol used for rescue and maintenance, the overall daily intake of formoterol was low, with 96.1% of all treatment days (n = 2452) covered by a total daily dose (regular + rescue) of 48 |ig (four doses) or less. There was no increase in the average daily intake of rescue formoterol over time. The clinical efficacy associated with this regimen was maintained over time and, in the case of morning peak expiratory flow rate, steadily improved over time. The Foradil Aerolizer inhalation system is simple to use and has a low resistance to inspiratory airflow that maximises the patient's control over dosing, while minimising the risk of under- and overdosing. These features may be especially valuable in a young patient population.

OBJECTIVES:To 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).DESIGN:A double-blind, double-dummy, multicentre, randomized, placebo controlled, single-dose, five-period crossover study.SETTING:Five centres in four countries - one centre each in France, Greece and Italy, and two centres in the Netherlands.PATIENTS:Forty-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).INTERVENTIONS:Patients 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.MAIN RESULTS:The 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.CONCLUSIONS:Formoterol is associated with a faster onset of bronchodilation than salmeterol in patients with COPD.

Salmeterol and formoterol are both beta 2-agonist bronchodilators with a long duration of action and are often classified together, yet they are distinctly different in their pharmacology. Recent evidence suggests there is a subpopulation of asthmatic patients who do not respond to salmeterol, yet can attain clinical benefit with formoterol. Following a literature search, three published case reports are reviewed as well as results from two published clinical trials designed specifically to document response to formoterol in 'non-responders to salmeterol' asthmatics. Possible mechanisms underlying this observation are discussed, including pharmacological differences of the two drugs relating to agonism at the beta 2-receptor and to effect on nuclear transcription factors.

This randomised, multicentre, parallel-group study compared the clinical efficacy and ease of handling of two dry powder inhalers delivering the long-acting beta 2-agonist formoterol. After run-in, 200 asthmatics on treatment with inhaled corticosteroids and still presenting with suboptimal asthma control were randomised to receive 12 micrograms formoterol twice daily via either the Aerolizer inhaler (Foradil Aerolizer) or the Turbuhaler inhaler (Oxis Turbuhaler) for four weeks. Study variables included the mean morning pre-medication peak expiratory flow (PEF) during the last seven days of treatment and the correct inhaler handling according to inhaler-specific checklists. The mean difference in the effect on morning pre-medication PEF was 13.86 l/min in favour of formoterol via the Aerolizer inhaler (90% confidence interval 2.50, 25.21) in the intent-to-treat population. Eighty-six per cent of the patients under treatment with formoterol via the Turbuhaler inhaler performed correctly all the essential inhalation manoeuvres, whereas 98% of those on the Aerolizer inhaler did so. These results strongly suggest similar clinical efficacy with twice daily treatment of formoterol 12 micrograms metered dose delivered either by the Aerolizer, or the Turbuhaler device. They also suggest that handling the Aerolizer is easier than that of the Turbuhaler.

Formoterol fumarate is a beta2-agonist bronchodilator that combines a fast onset of action with a long duration of action. Its fast onset of action is well documented in asthma but has not been directly compared with that of salbutamol in patients with chronic obstructive pulmonary disease (COPD). This randomized, double-blind, placebo-controlled study was conducted to assess the bronchodilatory effects over the first 3 h after inhalation of single doses of formoterol 24 microg delivered via the Aerolizer dry powder inhaler device (double-blind), or salbutamol 400 microg delivered by a Diskhaler dry powder inhaler (single-blind) in patients with COPD. A total of 24 patients with COPD were randomized [mean age 61.6 +/- 7.8 years, mean forced expiratory volume in 1 sec (FEV1) 1.38 +/- 0.32 l and 45.8 +/- 9.6% of predicted]. Inhalation of formoterol or salbutamol resulted in similar increases in FEV from 0 to 3 h post-dose. Both drugs produced similar bronchodilation by 5 min, which became almost maximal by 30 min. The primary efficacy variable, the area under the curve (AUC) of the FEV increase above predose baseline from 0 to 30 min (AUC(0-30 min)), demonstrated significant effects for formoterol (mean 5.89 +/- 4.67 l min(-1)), and salbutamol (mean 6.06 +/- 4.34 l min(-1)), which were not statistically different from each other but statistically significantly higher (P<0.0001) than that observed with placebo (-0.32 +/- 2.59 l min(-1)). In addition, both formoterol and salbutamol produced similar and rapid increases in forced vital capacity (FVC). In summary, this study confirms the rapid onset of action of formoterol and indicates that the onset of action of formoterol and salbutamol are similar in patients with COPD.

STUDY OBJECTIVES To compare the efficacy of adding formoterol or salbutamol to regular ipratropium bromide treatment in COPD patients whose conditions were suboptimally controlled with ipratropium bromide alone. DESIGN A randomized, double-blind, double-dummy, two-period, crossover clinical trial. SETTING Twenty-four clinics and university medical centers in nine countries. PATIENTS One hundred seventy-two patients with baseline FEV(1) < or = 65% predicted, with FEV(1) reversibility to salbutamol not exceeding the normal variability of the measurement, and symptomatic despite regular treatment with ipratropium bromide. INTERVENTIONS Each patient received two treatments in random order: either inhaled formoterol dry powder, 12 microg bid, in addition to ipratropium bromide, 40 microg qid for 3 weeks, followed by salbutamol, 200 microg qid, in addition to ipratropium, 40 microg qid for 3 weeks, or vice versa. MEASUREMENTS AND RESULTS Efficacy end points included morning premedication peak expiratory flow (PEF) during the last week of treatment (primary end point), the area under the curve (AUC) for FEV(1) measured for 6 h after morning dose on the last day of treatment, and symptom scores (from daily diary recordings). Morning PEF and the AUC for FEV(1) were significantly better for formoterol/ipratropium than for salbutamol/ipratropium (p = 0.0003 and p < 0.0001, respectively). The formoterol/ipratropium combination also induced a greater improvement in mean total symptom scores (p = 0.0042). The safety profile of the two treatments was comparable. CONCLUSIONS In COPD patients requiring combination bronchodilator treatment, the addition of formoterol to regular ipratropium treatment is more effective than the addition of salbutamol.