Formoterol as dry powder oral inhalation compared with salbutamol metered-dose inhaler in acute exacerbations of chronic obstructive pulmonary disease.
BACKGROUND
Acute exacerbations of chronic obstructive pulmonary disease (COPD) are managed with increased doses or frequency of the patient's existing bronchodilator therapy. The use of formoterol in the treatment of mild acute exacerbations of COPD has been suggested; however, a comparison of cumulative doses of formoterol with salbutamol, the gold standard bronchodilator agent for this pathologic condition, is still lacking.


OBJECTIVE
The aim of the study was to compare the inhaled beta2-agonists salbutamol (rapid onset, short duration of action) and formoterol (rapid onset, long duration of action), both used as needed in patients attending outpatient clinics because of mild acute exacerbations of COPD (Anthonisen exacerbation type I or II).


METHODS
A dose-response curve to formoterol via Turbuhaler or salbutamol via pressurized metered-dose inhaler (pMDI) was constructed. On 2 consecutive days, the patients received, in randomized order, both of the following active dose regimens: A = 12 + 12 + 24 microg formoterol via Turbuhaler (48-microg cumulative metered dose); B = 200 + 200 + 400 microg salbutamol via pMDI (800-microg cumulative metered dose). Dose increments were given at 30-minute intervals, with measurements made 25 minutes after each dose. The maximum forced expiratory volume in 1 second (FEV1) value during the dose-response curve to formoterol or salbutamol was chosen as the primary outcome variable to compare the 2 treatments. Oxygen saturation by pulse oximetry (SpO2) and pulse rate were also measured at each assessment period. Every adverse event, either reported spontaneously by the patients or observed by the investigators, was recorded.


RESULTS
Sixteen patients (2 women, 14 men) aged 51 to 77 years (most older than 65 years) participated in the study. Both formoterol and salbutamol induced a large, significant, dose-dependent increase in FEV1, inspiratory capacity (IC), and forced vital ca- pacity (FVC). There was no significant difference between FEV1, IC, and FVC values after 48 microg formoterol and 800 microg salbutamol. There was no significant difference in FEV1 after 24 microg formoterol and 800 microg salbutamol; however, the difference in FEV1 after 24 and 48 microg formoterol was significant. Neither heart rate (mean differences from baseline after 48 microg formoterol, 1.9 beats/min [95% CI, -3.4, 7.2] and 800 microg salbutamol, 3.7 beats/min [95% CI, -1.1, 8.5]) nor SpO2 (mean percentage differences from baseline after 48 microg formoterol, -0.37% [95% CI, -1.22, 0.47] and 800 microg salbutamol, -0.75% [95% CI, -1.73, 0.23]) changed significantly. However, SpO2 decreased below 90% in 2 patients after the highest dose of formoterol and in 1 patient after the highest dose of salbutamol.


CONCLUSIONS
In this small, selected group of patients with mild acute exacerbations of COPD, formoterol via Turbuhaler induced a fast bronchodilation that was dose dependent and not significantly different from that caused by salbutamol. Furthermore, formoterol appeared to be as well tolerated as salbutamol.
Cazzola
M
M
Department of Respiratory Medicine, A. Cardarelli Hospital, Naples, Italy. mcazzola@qubisoft.it
D'Amato
M
M
Califano
C
C
Di Perna
F
F
Calderaro
E
E
Matera
M G
MG
D'Amato
G
G
D000280:Administration, Inhalation; D000368:Aged; D000420:Albuterol / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004983:Ethanolamines / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D005541:Forced Expiratory Volume; D000068759:Formoterol Fumarate; D006801:Humans; D008297:Male; D008875:Middle Aged; D009330:Nebulizers and Vaporizers; D010092:Oximetry; D010101:Oxygen Consumption / Q000502:physiology; D011208:Powders; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D016037:Single-Blind Method; D012907:Smoking / Q000503:physiopathology; D014797:Vital Capacity
D001993:Bronchodilator Agents; D004983:Ethanolamines; D011208:Powders; D000420:Albuterol; D000068759:Formoterol Fumarate