Regular Article| Volume 95, ISSUE 11, P917-921, November 2001

Formoterol Turbuhaler®for as-needed therapy in patients with mild acute exacerbations of COPD

      This paper is only available as a PDF. To read, Please Download here.


      Worsening of underlying bronchospasm may be associated with acute exacerbations of chronic obstructive pulmonary disease (COPD). As airway obstruction becomes more severe, the therapeutic option is to add a short-acting inhaledβ2 -agonist as needed to cause rapid relief of bronchospasm. Unfortunately, however, the most effective dosage may increase above that recommended during acute exacerbations. Formoterol (Oxis®) Turbuhaler®has a rapid onset of action (within minutes) and demonstrates a maintained effect on airway function. In this study, we examined the effects of formoterol used as needed in 20 patients with acute exacerbations of COPD. A dose–response curve to inhaled formoterol (9 μ g per inhalation) or placebo was constructed using three separate inhalations, i.e. a total cumulative dose of 27 μ g. Dose increments were given at 20-min intervals, with measurements being made 15 min after each dose. Formoterol, but not placebo, induced a large and significant (P<0·001) dose-dependent increase in forced expiratory volume in 1 sec (FEV1) [mean differences from baseline = 0·1311 after 9 μ g formoterol (95% Cl: 0·096–0·167)] 0·181 1 after 18μ g formoterol (95% Cl: 0·140–0·222 1) and 0·208 1 after 27 μ g formoterol (95% Cl: 0·153–0·2631). However, 27 μ g formoterol did not induce further benefit [0·0271 (95% Cl: −0·008–0·062 1);P= 0·121] when compared with 18 μ g formoterol. Results of this study suggest the use of higher than customary dose of formoterol for as-needed therapy to provide rapid relief of bronchospasm in patients suffering from acute exacerbations of partially reversible COPD.




        • Tweeddale PM
        • Alexander F
        • McHardy G JR
        Short term variability in FEV1and bronchodilator responsiveness in patients with obstructive ventilatory defects.
        Thorax. 1987; 42: 487-490
        • Ikeda A
        • Nishimura K
        • Izumi T
        Pharmacological treatment in acute exacerbations of chronic obstructive pulmonary disease.
        Drugs Aging. 1998; 12: 129-137
        • Fromm Jr, RE
        • Varon J
        Acute exacerbations of obstructive lung disease. What to do when immediate care is crucial.
        Postgrad Med. 1994; 95: 101-106
      1. Am J Respir Crit Care Med. 1995; 152: 77S-120S
        • Emerman CL
        • Cydulka RK
        Effect of different albuterol dosing regimens in the treatment of acute exacerbation of chronic obstructive pulmonary disease.
        Ann Emerg Med. 1997; 29: 474-478
        • Jaeschke R
        • Guyatt GH
        • Cook D
        The effect of increasing doses of β -agonists on airflow in patients with chronic airflow limitation.
        Respir Med. 1993; 87: 433-438
        • Newhouse N
        • Dolovich M
        Aerosol therapy: nebulized vs metered dose inhaler.
        Chest. 1987; 91: 799-800
        • Barclay J
        • Whiting B
        • Addis GJ
        The influence of theophylline on maximal response to salbutamol in severe chronic obstructive pulmonary disease.
        Eur J Clin Pharmacol. 1982; 22: 389-393
        • Prior JG
        • Cochrane GM
        Assessment of optimum dose of inhaler terbutaline in patients with chronic asthma: the use of simple cumulative dose–response curves.
        Br J Dis Chest. 1982; 72: 266-268
        • Corris PA
        • Neville E
        • Nariman S
        Dose-response study of inhaled salbutamol powder in chronic airflow obstruction.
        Thorax. 1983; 38: 292-296
        • Karpel JP
        • Pesin J
        • Gentry E
        A comparison of the effects of ipratropium bromide and metaproterenol sulfate in acute exacerbations of COPD.
        Chest. 1990; 98: 835-839
        • Lloberes P
        • Ramis L
        • Montserrat JM
        Effect of three different bronchodilators during an exacerbation of chronic obstructive pulmonary disease.
        Eur Respir J. 1988; 1: 536-539
        • Bernasconi M
        • Brandolese R
        • Poggi R
        Dose–response effects and time course of effects of inhaled fenoterol on respiratory mechanics and arterial oxygen tension in mechanically ventilated patients with chronic airflow obstruction.
        Int Care Med. 1990; 16: 108-114
        • Siefkin AD
        Optimal pharmacologic treatment of the critically ill patient with obstructive airways disease.
        Am J Med. 1996; 100: 54S-61S
        • Calverley P MA
        Symptomatic bronchodilator treatment.
        in: Calverley P MA Pride NB Chronic Obstructive Pulmonary Disease. Chapman and Hall, London1995: 419-445
        • Cazzola M
        • Spina D
        • Matera MG
        The use of bronchodilators in stable chronic obstructive pulmonary disease.
        Pulm Pharmacol Ther. 1997; 10: 129-144
        • Cazzola M
        • Matera MG
        • Santangelo G
        Salmeterol and formoterol in partially reversible severe chronic obstructive pulmonary disease: a dose–response study.
        Respir Med. 1995; 89: 357-362
        • Ullman A
        • Löfdahl CG
        • Melander B
        Formoterol inhaled as dry powder or via pressurized metered-dose inhaler in a cumulative dose–response study.
        Allergy. 1996; 51: 745-748
        • Jeppsson AB
        • Nilsson E
        • Waldeck B
        Formoterol and salmeterol are both long acting compared to terbutaline in the isolated perfused and ventilated guinea-pig lung.
        Eur J Pharmacol. 1994; 257: 137-143
        • Faulds D
        • Hollingshead LM
        • Goa KL
        Formoterol. A review of its pharmacological properties and therapeutic potential in reversible obstructive airways disease.
        Drugs. 1991; 42: 115-137
        • Ringdal N
        • Derom E
        • Wahlin-Boll E
        Onset and duration of action of single doses of formoterol inhaled via Turbuhaler.
        Respir Med. 1998; 92: 1017-1021
        • Cazzola M
        • Santangelo G
        • Piccolo A
        Effect of salmeterol and formoterol in patients with chronic obstructive pulmonary disease.
        Pulm Pharmacol. 1994; 7: 103-107
        • Maesen BL
        • Westermann CJ
        • Duurkens VA
        Effects of formoterol in apparently poorly reversible chronic obstructive pulmonary disease.
        Eur Respir J. 1999; 13: 1103-1108
      2. Thorax. 1997; 52: 1S-28S
        • Rodriguez-Roisin R
        Toward a consensus definition for COPD exacerbations.
        Chest. 2000; 117: 398S-401S
      3. Am Rev Respir Dis. 1987; 136: 1285-1298
      4. Veteran Health Administration Clinical Practice Guideline for the Management of Person with COPD or Asthma,

        • Berg E
        In vitro properties of pressurized metered dose inhalers with and without spacer devices.
        J Aerosol Med. 1995; 83: 3S-10S
        • Tönnesen F
        • Laursen LC
        • Evald T
        Bronchodilating effect of terbutaline powder in acute severe bronchial obstruction.
        Chest. 1994; 105: 697-700
        • Löfdahl CG
        • Andersson L
        • Bondesson E
        Differences in bronchodilating potency of salbutamol in Turbuhaler as compared with a pressurized metered-dose inhaler formulation in patients with reversible airway obstruction.
        Eur Respir J. 1997; 10: 2474-2478
        • Borgstrom L
        • Derom E
        • Stahl E
        The inhalation device influences lung deposition and bronchodilating effect of terbutaline.
        Am J Respir Crit Care Med. 1996; 153: 1636-1640
        • Maesen FP
        • Costongs R
        • Smeets SJ
        Formoterol as dry powder inhalation.
        Chest. 1992; 101: 1376-1381