The Repeatability of Inspiration Performance Through Different Inhalers in Patients with Chronic Obstructive Pulmonary Disease and Control Volunteers

Abstract

Background: Inhalation therapy is a cornerstone of treating patients with chronic obstructive pulmonary disease (COPD). Inhaler types and through-device inhalation parameters influence airway drug delivery. We aimed to measure the repeatability of inhalation performance through four different commercially available inhalers. Methods: We recruited control subjects (n = 22) and patients with stable COPD (S-COPD, n = 16) and during an acute exacerbation (AE-COPD, n = 15). Standard spirometry was followed by through-device inhalation maneuvers using Ellipta^®, Evohaler^®, Respimat^®, and Genuair^®. Through-device inspiratory vital capacity (IVC_d) and peak inspiratory flow (PIF_d), as well as inhalation time (t_in) and breath hold time (t_bh), were recorded and all measurements were repeated in a random manner. Results: There was no difference in forced expiratory volume in 1 second (FEV₁) between patients (S-COPD: 39 ± 5 vs. AE-COPD: 32% ± 5% predicted, p > 0.05). In controls, the IVC_d was significantly reduced by all four devices in comparison with the slight reduction seen in COPD patients. In all subjects, PIF was lowered when inhaling through the devices in order of decreasing magnitude in PIF_d: Evohaler, Respimat, Ellipta, and Genuair. The Bland-Altman analysis showed a highly variable coefficient of repeatability for IVC_d and PIF_d through the different inhalers for all COPD patients. Based on the intermeasurement differences in patients, Respimat and Genuair showed the highest repeatability for IVC_d, while Genuair and Ellipta performed superior with regard to PIF_d. Conclusions: Our study is the first to compare repeatability of inhalation performances through different inhalers in COPD patients, showing great individual differences for parameters influencing lung deposition of inhaled medication from a given device. Our data provide new insight into the characterization of inhaler use by patients with COPD, and might aid the selection of the most appropriate devices to ensure the adequate and consistent delivery of inhaled drugs.

Keywords: COPD; exacerbation; inhalation device; inhaled therapy; repeatability.

FIG. 1.

Measurement configuration attached to Genuair^®. (A) Bacterial filter, (B) flowmeter, (C) metal ring with rubber overlay, (D) inhaler device, (E) spirometer. Color images are available online.

FIG. 2.

Bland-Altman analysis for Ellipta^®. The X-axis represents the mean of the two measurements for IVC_d and PIF_d, while the Y-axis shows the difference of the repeated measurements (first measurement–second measurement). Each dot represents a person. The dashed line shows the average of the difference for all subjects. IVC_d, through-device inspiratory vital capacity; LoA, Bland-Altman 95% limits of agreement; Meas, measurement; PIF_d, through-device peak inspiratory flow.

FIG. 3.

Bland-Altman analysis for Evohaler^®. The X-axis represents the mean of the two measurements for IVC_d and PIF_d, while the Y-axis shows the difference of the repeated measurements (first measurement–second measurement). Each dot represents a person. The dashed line shows the average of the difference for all subjects.

FIG. 4.

Bland-Altman analysis for Respimat^®. The X-axis represents the mean of the two measurements for IVC_d and PIF_d, while the Y-axis shows the difference of the repeated measurements (first measurement–second measurement). Each dot represents a person. The dashed line shows the average of the difference for all subjects.

FIG. 5.

Bland-Altman analysis for Genuair. The X-axis represents the mean of the two measurements for IVC_d and PIF_d, while the Y-axis shows the difference of the repeated measurements (first measurement–second measurement). Each dot represents a person. The dashed line shows the average of the difference for all subjects.

FIG. 6.

Repeatability sequence summary for the four inhalers. (A) All-COPD IVC_d (n = 20). (B) All-COPD PIF_d (n = 20). (C) Control IVC_d (n = 22). (D) Control PIF_d (n = 22). By each control subject and patient, a rank number between 1 and 4 was associated with each inhaler regarding the magnitude of the difference between the two values for PIF_d and IVC_d, respectively. Rank 1 was given to the device with the lowest difference between the two inspiratory measurements followed by Rank 2, 3, and 4. On the figure, rank numbers are shown by four edges of the axes with blue color, and the sum of subjects with a certain rank is indicated on the axes. COPD, chronic obstructive pulmonary disease. Color images are available online.