The use of plethysmography and oscillometry to compare long‐acting bronchodilators in patients with COPD

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. AIMSAssessment 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. METHODSIn this double-blind, randomized, four-way crossover study, 32 COPD patients received single doses of Tio (18 mg), S (50 and 100 mg) 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. RESULTSTio 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. CONCLUSIONSsGaw 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.

Effect of bronchodilation on expiratory flow limitation and resting lung mechanics in COPD

“…Noninvasive measurements of tidal lung mechanics using the forced oscillation method are an attractive alternative to more usual effort dependent tests of pulmonary function and others have shown that such tests are a sensitive way of detecting bronchodilator effects in these patients [41]. However, the change in the total Zrs after a bronchodilator may underestimate the true effects of therapy if expiratory impedance data are not excluded from the analysis in flow-limited patients.…”

Superiority of "triple" therapy with salmeterol/fluticasone propionate and tiotropium bromide versus individual components in moderate to severe COPD

“…Based on previous data, 18 a treatment decrease of 15% in sGaw on the individual treatments compared with the combination was defined as clinically relevant. To detect a decrease of 15% in AUC (0-4 h) sGaw between one of the individual treatments and SFC+TIO with 90% power, a two sided 0.025 significance level and a within subject SD of 0.1652 (log transformed sGaw), it was estimated that 30 subjects would be required to complete at least two active treatment periods.…”

“…We used the sensitive pulmonary function measurement of specific airway conductance as the primary end point to compare the different treatment regimens. [18][19][20][21] Pulmonary function measurements of spirometry and lung volumes were also performed, and symptom scores were evaluated.…”

Update on the roles of distal airways in COPD

“…Finally, it was recently shown that ''distal'' oscillometry parameters (R5Hz-R20Hz and X5Hz), measured at baseline breathing and at an elevated respiratory rate (40 breaths?min -1 ), correlated perfectly with the fall of dynamic compliance at 60 breaths?min -1 , a reference invasive technique used to assess the distal airways [124]. Impulse oscillometry is also useful for evaluating responses to short-and long-acting bronchodilators and here it is suggested to be more sensitive than spirometry in comparing drugs [125,126]. The clinical relevance of oscillometry parameters in COPD was recently analysed by HARUNA et al [127].…”