The use of plethysmography and oscillometry to compare long‐acting bronchodilators in patients with COPD
Open Access
- 15 September 2007
- journal article
- research article
- Published by Wiley in British Journal of Clinical Pharmacology
- Vol. 65 (2), 244-252
- https://doi.org/10.1111/j.1365-2125.2007.03013.x
Abstract
What is already known about this subject • Forced expiratory voume in 1 s (FEV1) is the standard measurement used to measure drug effects in chronic obstructive pulmonary disease (COPD) clinical trials. • Having previously shown that specific airway conductance (sGaw) measured using body plethysmography and impulse oscillometry (IOS) are more sensitive than FEV1 for assessing short‐acting bronchodilator effects in patients with COPD, we conducted the first randomized, placebo‐controlled study to compare long‐acting bronchodilators in COPD patients using these techniques. What this study adds • sGaw and IOS sensitively differentiated between the effects of tiotropium and salmeterol when FEV1 measurements were similar. • sGaw and IOS measurements are better than FEV1 for sensitively assessing bronchodilator pharmacology and differentiating between treatments in COPD clinical trials. Aims Assessment of bronchodilator pharmacology in chronic obstructive pulmonary disease (COPD) may be improved by using more sensitive methods than spirometry, such as impulse oscillometry (IOS) and body plethysmography. We sought to compare salmeterol (S) and tiotropium (Tio) using these methods. Methods In this double‐blind, randomized, four‐way crossover study, 32 COPD patients received single doses of Tio (18 µg), S (50 and 100 µg) or placebo. Specific airway conductance (sGaw), forced expiratory volume in 1 s (FEV1) and IOS were measured pre‐ and up to 26 h postdose. Comparisons between treatments were analysed by weighted means (WM) between 0 and 12 (WM 0–12 h) and 12–24 h (WM 12–24 h) postdose. Data are expressed as mean difference (or geometric ratio for nonparametric data) with 95% confidence intervals. Results Tio and S100 significantly improved FEV1, sGaw and IOS parameters up to 26 h and S50 up to 16 h. WM analysis showed no difference between Tio and S100 in FEV1 for 0–12 h or 12–24 h. Maximum mid‐expiratory flow (−0.06; −0.11, −0.01) and R35 (0.02; 0.01, 0.03) demonstrated superiority of S100 compared with Tio for WM 0–12 h sGaw (1.12; 1.02, 1.23), R5 (−0.06; −0.09, −0.02), R15 (−0.03; −0.05, −0.01), and resonant frequency (RF) (−2.30; −3.83, −0.77) showed superiority of Tio compared with S100 for WM 12–24 h. At 26 h, sGaw, R5, R15, X5 and RF also showed superiority of Tio compared with S100. Conclusions sGaw and IOS parameters sensitively differentiated between the effects of Tio and S when FEV1 measurements were similar. Clinical trials in patients with COPD should use IOS and sGaw to assess comprehensively bronchodilator pharmacology.This publication has 22 references indexed in Scilit:
- Plethysmography and impulse oscillometry assessment of tiotropium and ipratropium bromide; a randomized, double-blind, placebo-controlled, cross-over study in healthy subjectsBritish Journal of Clinical Pharmacology, 2006
- Measuring bronchodilation in COPD clinical trialsBritish Journal of Clinical Pharmacology, 2005
- A comparison of lung function methods for assessing dose–response effects of salbutamolBritish Journal of Clinical Pharmacology, 2004
- Detection of expiratory flow limitation in COPD using the forced oscillation techniqueEuropean Respiratory Journal, 2004
- Bronchodilator reversibility testing in chronic obstructive pulmonary diseaseThorax, 2003
- Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary DiseaseAmerican Journal of Respiratory and Critical Care Medicine, 2001
- Airway and Lung Tissue Mechanics in AsthmaAmerican Journal of Respiratory and Critical Care Medicine, 1999
- Respiratory system reactance as an indicator of the intrathoracic airway response to methacholine in childrenPediatric Pulmonology, 1996
- Assessment of reversibility of airflow obstruction.American Journal of Respiratory and Critical Care Medicine, 1994
- Volume Adjustment of Maximal Midexpiratory FlowSocial psychiatry. Sozialpsychiatrie. Psychiatrie sociale, 1980