Allergy Asthma Immunol Res.  2020 May;12(3):454-466. 10.4168/aair.2020.12.3.454.

Efficacy and Safety of a Pressurized Metered-Dose Inhaler in Older Asthmatics: Comparison to a Dry Powder Inhaler in a 12-Week Randomized Trial

• Woo SD
• Ye YM
• Lee Y
• Lee SH
• Shin YS
• Park JH
• Choi H
• Lee HY
• Shin HJ
• Park HS

• KMID: 2471229
• DOI: http://doi.org/10.4168/aair.2020.12.3.454

Abstract

PURPOSE
Asthma control in older asthmatics is often less effective, which may be attributed to small airway dysfunction and poor inhalation technique. We compared the efficacy of 2 inhalers (fluticasone propionate/formoterol treatment using a pressurized metered-dose inhaler [p-MDI group] vs. fluticasone propionate/salmeterol treatment using a dry powder inhaler [DPI group]) in older asthmatics.
METHODS
We conducted a 12-week, randomized, open-label, parallel-designed trial in older patients (over 55 years old) with moderate-to-severe asthma, and compared the efficacy and safety for asthma control between the 2 groups. Subgroup analyses on disease duration and air trapping were performed. Clinical parameters, including changes in lung function parameters, inhaler technique and adherence, were compared with monitoring adverse reactions between the 2 groups.
RESULTS
A total of 68 patients underwent randomization, and 63 (30 in the p-MDI group and 33 in the DPI group) completed this study. The p-MDI group was non-inferior to the DPI group with regard to the rate of well-controlled asthma (53.3% vs. 45.5%, P < 0.001; a predefined non-inferiority limit of 17%). In subgroup analyses, the proportion of patients who did not reach well-controlled asthma in the p-MDI group was non-inferior to that in the DPI group; the difference was 12.7% among those with a longer disease duration (≥ 15 years) and 17.5% among those with higher air-trapping (RV/TLC ≥ 45%), respectively (a predefined non-inferiority limit of 17%, P < 0.001). No significant differences were observed in lung function parameters, inhalation techniques, adherence and adverse reactions between the 2 groups.
CONCLUSION
These results suggest that the p-MDI group may be comparable to the DPI group in the management of older asthmatics in aspects of efficacy and safety.

Keyword

Asthma; aged; metered dose inhalers; dry powder inhalers; airway management; medication adherence

MeSH Terms

Airway Management
Asthma
Dry Powder Inhalers*
Fluticasone
Humans
Inhalation
Lung
Medication Adherence
Metered Dose Inhalers
Nebulizers and Vaporizers*
Random Allocation
Fluticasone

Figure

• 

  Fig. 1 Trial design and CONSORT flow.(A) shows the design of the trial and (B) shows the screening, randomization, and treatment for patients stratified according to asthma duration (≥ 15 years or < 15 years). All patients who underwent randomization into the treatment method were included in the full analysis set population.CONSORT, Consolidated Standards Of Reporting Trials; p-MDI, pressurized metered-dose inhalers; FP/FOR, fluticasone propionate/formoterol fumarate; DPI, dry powder inhalers; FP/SAL, fluticasone propionate/salmeterol xinafoate.

• 

  Fig. 2 The proportion of asthma control status in the p-MDI and DPI groups during the study period.Asthma control status was assessed according to the GINA guidelines. The proportion test (one-sided) for proving non-inferiority of the FP/FOR group and the FP/SAL group in the PP population, with a predetermined non-inferiority margin of −17.0% for the difference in the rates of well-controlled asthma between the 2 groups. PP principle was applied to reduce possible statistical bias caused by missing data imputation.p-MDI, pressurized metered-dose inhalers; FP/FOR, fluticasone propionate/formoterol fumarate; DPI, dry powder inhalers; FP/SAL, fluticasone propionate/salmeterol xinafoate; GINA, Global Initiative for Asthma; PP, per-protocol; CI, confidence interval.

• 

  Fig. 3 Subgroup analyses of the risk of “partly controlled asthma” or “uncontrolled asthma” according to baseline asthma duration and baseline air trapping.The subgroup analyses were evaluated in the per-protocol population to reduce possible statistical biases caused by missing data imputation.p-MDI, pressurized metered dose inhalers; FP/FOR, fluticasone propionate/formoterol fumarate; DPI, dry powder inhalers; FP/SAL, fluticasone propionate/salmeterol xinafoate; RR, relative risk; CI, confidence interval; RV/TLC, residual volume/total lung capacity.

• 

  Fig. 4 Changes in total inhaler technique scores from baseline to week 12.Inhaler technique scores were calculated from the sum of checklist scores. The P values shown refer to change from baseline using the paired t-test or Wilcoxon signed rank test.p-MDI, pressurized metered-dose inhalers; FP/FOR, fluticasone propionate/formoterol fumarate; DPI, dry powder inhalers; FP/SAL, fluticasone propionate/salmeterol xinafoate.*P < 0.01 and †P < 0.001. I bars represent 95% confidence intervals.

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