A comparison of lung function methods for assessing dose–response effects of salbutamol

• Published in: British journal of clinical pharmacology Vol. 58; no. 2; pp. 134 - 141
• Main Authors: Houghton, Catherine M., Woodcock, Ashley A., Singh, Dave
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.08.2004; Blackwell Science; Blackwell Science Inc
• Subjects: Adult; Aged; Albuterol - administration & dosage; Asthma - drug therapy; Asthma - physiopathology; Biological and medical sciences; Bronchodilator Agents - administration & dosage; Dose-Response Relationship, Drug; Female; Forced Expiratory Volume - physiology; Humans; lung function tests; Male; Medical sciences; Middle Aged; Pharmacodynamics; Pharmacology. Drug treatments; Pulmonary Disease, Chronic Obstructive - drug therapy; Pulmonary Disease, Chronic Obstructive - physiopathology; Respiratory system; reversibility technique; Human; Spirometry; Agonist; Respiratory disease; Bronchodilator; β2-Adrenergic receptor; β-Adrenergic receptor agonist; Asthma; Dose activity relation; lung function test; Chemotherapy; Lung function; Treatment; reversibility technique; Salbutamol; Obstructive pulmonary disease; Pharmacokinetics; Comparative study; Oscillometry; Plethysmography
• ISSN: 0306-5251; 1365-2125
• DOI: 10.1111/j.1365-2125.2004.02105.x

Pulmonary function methods which are able to detect small pharmacological effects may be useful for assessing the full dose–response curve of bronchodilatators. We compared the ability of impulse oscillometry (R5, R20, X5, RF), plethysmography (sGaw) and spirometry [forced expiratory volume in 1 s (FEV1), maximal mid expiratory flow rate (MMEF)] to measure the dose–response effects of salbutamol in 12 healthy subjects, 12 mild asthmatics (mean FEV1 96% predicted) and 12 moderate asthmatics (mean FEV1 63% predicted). The techniques were performed twice to assess variability. Then salbutamol 10, 20, 100, 200 and 800 µg was administered. The sensitivity of the methods were compared by determining the lowest dose that caused changes greater than variability. In healthy subjects significant changes (p ≤ 0.05) were observed only in FEV1 (4.1%) and MMEF (14.6%) at 100 µg and sGaw (25.6%) and R20 (8.3%) at 200 µg. In mild asthmatics significant changes were observed in sGaw (15.9%) at 10 µg, X5 (23%), RF (20.3%) and MMEF (15.7%) at 20 µg, R5 (13.9%) and R20 (9.4%) at 100 µg and FEV1 (7.1%) at 200 µg. All measurements except R20 demonstrated significant changes at 10 µg in moderate asthmatics. The most sensitive test for assessing bronchodilatation is different in healthy subjects and asthmatics, and varies with severity of airflow obstruction.