Therapeutic effect of long-acting muscarinic antagonist for treating uncontrolled asthma assessed using impulse oscillometry

Abstract

Background: In recent years, the incorporation of LAMAs into asthma therapy has been expected to enhance symptom control. However, a significant number of patients with asthma continue to experience poorly managed symptoms. There have been limited investigations on LAMA-induced airway alterations in asthma treatment employing IOS. In this study, we administered a LAMA to patients with poorly controlled asthma, evaluated clinical responses and respiratory function, and investigated airway changes facilitated by LAMA treatments using the IOS.

Methods: Of a total of 1282 consecutive patients with asthma, 118 exhibited uncontrolled symptoms. Among them, 42 switched their treatment to high-dose fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) (ICS/LABA/LAMA). The patients were then assessed using AHQ-33 or LCQ and ACT. Spirometry parameters (such as FEV₁ or MMEF) and IOS parameters (such as R20 or AX) were measured and compared before and after exacerbations and the addition of LAMA.

Results: Of the 42 patients, 17 who switched to FF/UMEC/VI caused by dyspnea exhibited decreased pulmonary function between period 1 and baseline, followed by an increase in pulmonary function between baseline and period 2. Significant differences were observed in IOS parameters such as R20, R5-R20, Fres, or AX between period 1 and baseline as well as between baseline and period 2. Among the patients who switched to inhaler due to cough, 25 were classified as responders (n = 17) and nonresponders (n = 8) based on treatment outcomes. Among nonresponders, there were no significant differences in spirometry parameters such as FEV₁ or PEF and IOS parameters such as R20 or AX between period 1 and baseline. However, among responders, significant differences were observed in all IOS parameters, though not in most spirometry parameters, between period 1 and baseline. Furthermore, significant differences were noted between baseline and period 2 in terms of FEV₁, %MMEF, %PEF, and all IOS parameters.

Conclusion: ICS/LABA/LAMA demonstrates superiority over ICS/LABA in improving symptoms and lung function, which is primarily attributed to the addition of LAMA. Additionally, IOS revealed the effectiveness of LAMA across all airway segments, particularly in the periphery. Hence, LAMA can be effective against various asthma phenotypes characterized by airway inflammation, even in real-world cases.

Keywords: Bronchial asthma; Impulse oscillometry system (IOS); Long-acting muscarinic antagonist (LAMA); Pulmonary function test.

Fig. 1

Flowchart of the 1282 consecutive patients treated with ICS/LABA between April 2021 and March 2023. Of these patients, 118 who presented with uncontrolled asthma switched treatment. Moreover, 42 patients taking high-dose ICS/LABA switched to high-dose ICS/LAMA/LABA

Fig. 2

Definition of period 1, baseline, and period 2. Baseline was defined as the time of diagnosis of uncontrolled asthma, period 1 was defined as the time of diagnosis of controlled asthma before switching inhaler within 1 year, and period 2 was defined as 2 months after switching to triple therapy, indicating well controlled asthma

Fig. 3

Comparison of spirometry and impulse oscillometry data in patients with uncontrolled asthma caused by dyspnea. The differences between period 1 and baseline or between baseline and period 2 were analyzed using the unpaired t-test, *: p < 0.05, **: p < 0.01

Fig. 4

Comparison of spirometry and impulse oscillometry data in patients with uncontrolled asthma caused by cough. The differences between period 1 and baseline or between baseline and period 2 were analyzed using the unpaired t-test, *: p < 0.05, **: p < 0.01

Fig. 5

Comparison of therapeutic effects (Δ FEV₁: change in FEV₁ or Δ LCQ: change in LCQ) in asthma subtypes classified via impulse oscillometry. The asthma subtypes classified with IOS were defined using the equations reported by Vogel et al. According to the percentage predicted value of the IOS, four groups were defined as follows: the central type (open circle), defined as R20 ≥ 100% and R5–R20 < 100%; the peripheral type (closed circle), R20 < 100% and R5–R20 ≥ 100%; the mixed type (closed triangle), R20 ≥ 100% and R5–R20 ≥ 100%; and the resistless type (open triangle), R20 < 100% and R5–R20 < 100%. Differences among the subtypes were analyzed using nonrepeated analysis of variance