Effects of long-acting bronchodilators and prednisolone on inspiratory lung function parameters in stable COPD.

In chronic obstructive pulmonary disease (COPD), there is a poor correlation between forced expiratory volume in 1 s (FEV1) and dyspnea following bronchodilator use. Better correlations have been observed between inspiratory lung function parameters (ILPs) and dyspnea, which drives our interest in ILPs. However, the acute and prolonged effects of long-acting bronchodilators and oral corticosteroids on ILPs have not been well investigated. Therefore, the aim of this study was to investigate the effects of these treatments on the ILPs, FEV1, dyspnea (visual analog scale (VAS)) and clinical COPD questionnaire (CCQ). Twenty-eight stable COPD patients had their ILPs and FEV1 measured both before and 2 h after the use of a single dose of 18 mcg bronchodilator tiotropium and 50 mcg salmeterol. Thereafter, the patients were randomized to 2 weeks of treatment with 30 mg oral prednisolone once daily or oral placebo in combination with daily treatment with these two bronchodilators. Four weeks after the cessation of the randomized treatment, the ILPs and FEV1 were again measured. After each intervention, any change in the VAS score was assessed. With both bronchodilators, significant improvements in ILPs were demonstrated (p < 0.005), with the exception of changes in ILPs inspiratory capacity (IC) and forced inspiratory flow at 50% of the vital capacity (FIF50) after tiotropium inhalation. After 2 weeks of treatment with prednisolone, significant differences were found for ILP forced inspiratory volume in 1 s (FIV1) and FEV1 compared with placebo. These differences were no longer present 4 weeks after the cessation of prednisolone. Significant relationships between ILPs and VAS scores were only found after 2 weeks of treatment with prednisolone or placebo. After a single dose of long-acting bronchodilator salmeterol, significant improvements are observed in all ILPs and in FIV1 and PIF after tiotropium. Two weeks of oral corticosteroid treatment improved the FIV1 and FEV1. The dyspnea VAS score was only significantly correlated with the ILPs after 2 weeks of oral corticosteroid treatment.

Ramlal SK ，Visser FJ ，Hop WC ，Dekhuijzen PN ，Heijdra YF ... -  《-》

The effect of bronchodilators administered via aerochamber or a nebulizer on inspiratory lung function parameters.

In chronic obstructive pulmonary disease (COPD) the clinical efficacy of bronchodilator therapy delivered via a nebulizer versus an aerochamber on FEV1 is controversial. No studies comparing changes in inspiratory pulmonary function parameters (ILPs) using these inhaler devices are currently available. This information might be of interest because due to dynamic bronchial compression, the relationship between the ILPs and dyspnea is more reliable than that between FEV1 and dyspnea. Therefore, our study aimed to investigate whether changes in ILPs after use of these inhaler devices were similar to the changes in FEV1 and correlate with VAS (Visual Analogue Scale). Forty-one stable COPD patients participated in a crossover trial. Spirometry was performed before and after two puffs Combivent (200 mcg salbutamol and 20 mcg ipratropium per puff) using an aerochamber or 2 mL of Combivent (2.5 mg salbutamol and 250 mcg ipratropium per mL) using a nebulizer. Differences in lung function parameters and changes in VAS were measured. ILP values improved significantly from baseline after Combivent administration using both devices (p ≤ 0.004). With both devices, the mean percent changes were significantly greater for FEV(1) than the ILPs (p ≤ 0.003), except for IC (p = 0.19). The mean VAS score did not differ significantly between the devices (p = 0.33), but significant correlations were found between the VAS and forced inspiratory flow at 50% of the vital capacity (FIF(50)) and peak inspiratory flow (PIF) when a nebulizer was used. With an aerochamber, no significant correlations between lung function parameters and VAS were found. The present study demonstrates that ILPs improved significantly after using either device. Although significant correlations were found between the VAS and FIF(50) and PIF for the nebulizer, in stable COPD patients, the pMDI plus spacer is a better route of administration than a nebulizer.

Ramlal SK ，Visser FJ ，Hop WC ，Dekhuijzen PN ，Heijdra YF ... -  《-》

Reversibility of inspiratory lung function parameters after short-term bronchodilators in COPD.

The responsiveness of short-term bronchodilator use on inspiratory lung function parameters (ILPs), including Forced Inspiratory Volume in one second (FIV(1)), Inspiratory Capacity (IC), Forced Inspiratory Flow at 50% of the vital capacity (FIF(50)), Peak Inspiratory Flow (PIF) and on the relationship between these values and dyspnea in COPD subjects has been examined only sparsely in past studies. The aim of this study was to assess the effects of inhaled salbutamol 400 mcg, ipratropium 80 mcg and a placebo on ILP and FEV(1) and their relationship to dyspnea, as measured with a Visual Analogue Scale (VAS). A total of 85 subjects with stable COPD participated in a crossover, randomized, double-blind, placebo-controlled study. Spirometry was performed before and after inhalation of salbutamol, ipratropium or a placebo. The primary analysis was performed using 63 participants with absent reversibility. All ILP and FEV(1) values improved significantly after bronchodilator administration except for FIF(50) after ipratropium administration. After administration of both bronchodilators, the mean percent changes from initial values did not significantly differ between the various ILPs and FEV(1). The mean VAS score showed significant improvements after bronchodilator and placebo inhalation but did not significantly correlate with changes in lung function parameters. For each lung function parameter, patients were further classified as responders if the amount of change was greater than the coefficient of repeatability of the test. Response rates did not differ significantly between the various ILPs. Moreover, no significant differences were found between responders and non-responders with respect to dyspnea after bronchodilator inhalation. This finding applied to all ILP and FEV(1) values. In subjects with COPD, all ILP, FEV(1) values and VAS scores showed significant improvements after bronchodilator use as well as with placebo. However, ILPs were not more sensitive than FEV(1) for detecting responders after bronchodilator use or changes in the VAS score.

Ramlal SK ，Visser FJ ，Hop WC ，Dekhuijzen PN ，Heijdra YF ... -  《-》

Improved daytime spirometric efficacy of tiotropium compared with salmeterol in patients with COPD.

Briggs DD Jr ，Covelli H ，Lapidus R ，Bhattycharya S ，Kesten S ，Cassino C ... -  《PULMONARY PHARMACOLOGY & THERAPEUTICS》

Effects of long-acting bronchodilators in COPD patients according to COPD severity and ICS use.

Indacaterol is a once-daily, long-acting β(2)-agonist bronchodilator that improves dyspnoea and health status in patients with moderate-to-severe COPD. While its bronchodilator effects have been shown to be maintained in different patient subgroups, effects on clinical outcomes in certain subgroups are not yet defined. Post-hoc analysis of pooled clinical study data to investigate efficacy and safety of indacaterol compared with placebo and other long-acting bronchodilators (formoterol, salmeterol, open-label tiotropium) in patient subgroups defined by COPD severity (GOLD stage II or III; n = 4082) and ICS use at baseline (no/yes; n = 4088). Efficacy outcomes were trough (24-h post-dose) FEV(1), dyspnoea (transition dyspnoea index; TDI) and health status (St George's Respiratory Questionnaire; SGRQ) after 26 weeks. All active treatments significantly improved trough FEV(1) and dyspnoea compared with placebo, and all apart from open-label tiotropium improved health status compared with placebo. Among active treatments, indacaterol 150 μg had the best overall efficacy profile in the GOLD II and no-ICS subgroups. In the GOLD III and ICS subgroups, indacaterol 300 μg had the best overall efficacy, including a marked effect on dyspnoea (1.4-point improvement in TDI total score vs. placebo; p < 0.001). Within subgroups, the incidence of adverse events was similar between treatments. Indacaterol maintained its efficacy regardless of disease severity or use of concurrent ICS. Indacaterol 150 μg had the best overall efficacy profile in the GOLD stage II patients while, in patients with more severe disease, indacaterol 300 μg provided useful improvements in dyspnoea.

Decramer M ，Dahl R ，Kornmann O ，Korn S ，Lawrence D ，McBryan D ... -  《-》