A Randomized Controlled Trial To Assess the Optimal Dose and Effect of Nebulized Albuterol in Acute Exacerbations of COPD

doi:10.1378/chest.128.1.48

Chest

Volume 128, Issue 1, July 2005, Pages 48-54

https://doi.org/10.1378/chest.128.1.48 Get rights and content

Study objectives

Despite the widespread use of short-acting, inhaled β₂-agonists in acute exacerbations of COPD (AECOPDs), little is known about their optimal dose. The aims of this study are to compare the bronchodilator response to incremental doses of inhaled albuterol during and after recovery from an AECOPD, and to compare the effects of regular nebulized albuterol, 2.5 mg and 5 mg, on the speed of recovery.

Methods

Eighty-six patients admitted with an AECOPD were recruited. Each patient was administered incremental doses of inhaled albuterol on hospital admission and following recovery. Dose-response curves were constructed based on FEV₁ and peak expiratory flow rate (PEFR) recorded after each incremental dose. Patients were then randomized in a double-blind fashion to receive 2.5 mg or 5 mg of nebulized albuterol q4h until recovery. Twice-daily PEFR, the number of extra doses of bronchodilators, and side effects reported were recorded.

Results

Maximal bronchodilation (Emax) FEV₁ (maximal bronchodilatory response to albuterol) increased from 0.64 ± 0.27 L/min during the exacerbation to 0.94 ± 0.38 L/min during recovery (p < 0.001). The Emax PEFR increased from 147.53 ± 62.46 L/min to 222.94 ± 73.82 L/min after recovery (p = <0.001). There was no significant difference in rate of recovery of PEFR (p = 0.684), duration of hospital stay (p = 0.084), or side effects (p = 0.506) between the groups receiving 2.5 mg or 5 mg of nebulized albuterol.

Conclusions

There was significant improvement in Emax to inhaled albuterol as the COPD exacerbation resolved. There was no significant difference in outcomes including length of hospital stay or recovery of lung function between patients treated with regular 2.5 mg vs 5 mg of nebulized albuterol during an AECOPD.

Section snippets

Patients

This was a multicenter study done in the respiratory departments of four teaching hospitals in Yorkshire, England. Eighty-six patients admitted with an exacerbation of previously known COPD based on BTS criteria⁸ were recruited into the study. All patients had an FEV₁ < 80% of the predicted value with < 15% and/or 200-mL reversibility to inhaled bronchodilators. AECOPDs among patients admitted to hospital were diagnosed if two of the three factors were present, namely increased dyspnea,

Results

Among the 86 COPD patients admitted with acute exacerbation, there was slight female predominance (47 female and 39 male patients). The mean age of the patients was 69.26 ± 9.25 years (± SD) [range, 47 to 90 years], and the mean FEV₁ was 0.816 ± 0.41 L/min (range, 0.30 to 2.14 L/min; 18 to 70% of predicted). Table 1shows the characteristics of patients included in the study.

The study did not show any significant difference in terms of outcome between patient groups receiving 2.5 mg or 5 mg of

Discussion

This study demonstrates that there is no significant difference in clinical outcome in patients treated every 4 h with either 2.5 mg or 5 mg of nebulized albuterol throughout an AECOPD. These results compliment earlier reports of patients with stable COPD in which near-Emax occurred with smaller doses of nebulized terbutaline than those conventionally used over 12 weeks without development of drug tolerance.¹⁰ Fifty percent of Emax during AECOPD in this study was achieved with a cumulative dose

References (24)

C Teale et al.
Response to nebulised ipratropium bromide and terbutaline in acute severe asthma
Respir Med
(1992)
JB Cheng et al.
Comparison of muscarinic and β-adrenergic receptors between bovine peripheral lung and tracheal smooth muscles: a striking difference in receptor concentration
Life Sci
(1982)
TAR Seemungal et al.
Time course and recovery of exacerbations in patients with chronic obstructive pulmonary disease
Am J Respir Crit Care Med
(2000)
TAR Seemungal et al.
Effect of exacerbation on quality of life in patients with chronic obstructive pulmonary disease
Am J Respir Crit Care Med
(1998)
GC Donaldson et al.
Relationship between exacerbation frequency and lung function decline in chronic obstructive pulmonary disease
Thorax
(2002)
P Sestini et al.
Short-acting β₂-agonists for stable chronic obstructive pulmonary disease. The Cochrane Library
(2003)
MJ Belman et al.
Inhaled bronchodilators reduce dynamic hyperinflation during exercise in patients with chronic obstructive pulmonary disease
Am J Respir Crit Care Med
(1996)
EH Walters et al.
Optimal dose of salbutamol respiratory solution: comparison of three doses with plasma levels
Thorax
(1981)
JN Stainforth et al.
Dosage and delivery of nebulised β agonists in hospital
Thorax
(1983)
British Thoracic Society
BTS guidelines for the management of chronic obstructive pulmonary disease
Thorax
(1997)

National Institute for Clinical Excellence (NICE)

Chronic obstructive pulmonary disease: national clinical guideline for management of chronic obstructive pulmonary disease in adults in primary and secondary care

Thorax

(2004)

C Teale et al.

Regular nebulised terbutaline in chronic obstructive airways disease: dose-response studies fail to detect tolerance

Br J Clin Pharmacol

(1991)

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Chest

Clinical InvestigationsCopdA Randomized Controlled Trial To Assess the Optimal Dose and Effect of Nebulized Albuterol in Acute Exacerbations of COPD

Study objectives

Methods

Results

Conclusions

Section snippets

Patients

Results

Discussion

Respir Med

Life Sci

Time course and recovery of exacerbations in patients with chronic obstructive pulmonary disease

Am J Respir Crit Care Med

Effect of exacerbation on quality of life in patients with chronic obstructive pulmonary disease

Am J Respir Crit Care Med

Relationship between exacerbation frequency and lung function decline in chronic obstructive pulmonary disease

Thorax

Short-acting β2-agonists for stable chronic obstructive pulmonary disease. The Cochrane Library

Inhaled bronchodilators reduce dynamic hyperinflation during exercise in patients with chronic obstructive pulmonary disease

Am J Respir Crit Care Med

Optimal dose of salbutamol respiratory solution: comparison of three doses with plasma levels

Thorax

Dosage and delivery of nebulised β agonists in hospital

Thorax

BTS guidelines for the management of chronic obstructive pulmonary disease

Thorax

Chronic obstructive pulmonary disease: national clinical guideline for management of chronic obstructive pulmonary disease in adults in primary and secondary care

Thorax

Regular nebulised terbutaline in chronic obstructive airways disease: dose-response studies fail to detect tolerance

Br J Clin Pharmacol

Clinical Investigations
Copd
A Randomized Controlled Trial To Assess the Optimal Dose and Effect of Nebulized Albuterol in Acute Exacerbations of COPD

Short-acting β₂-agonists for stable chronic obstructive pulmonary disease. The Cochrane Library