4 1.4 Determining the Effectiveness of Triple versus Dual Therapy in ACO
Is Triple Therapy More Effective Than Dual Therapy?
To test if triple therapy is more effective than dual therapy in the treatment of ACO, a group of researchers decided to conduct a 12 week, randomized, open-label, crossover study. First, they had the participants take dual therapy for 4 weeks before the actual study began. Dual therapy consisted of 200 micrograms of fluticasone furoate (an inhaled corticosteroid) and 25 micrograms of vilanterol (a long-acting B2 agonist). Then, they randomized the participants to either dual therapy or triple therapy treatment groups at what they deemed “week 0”. Triple therapy consisted of dual therapy with 62.5 micrograms of umeclidinium (a long-acting muscarinic antagonist) added. Then, 4 weeks into the study, they switched the participants into the other treatment group, this was the crossover part of the study. The patients that were taking dual therapy now started taking triple therapy and the patients who were taking triple therapy were then given dual therapy. The researchers then monitored the participants in this new treatment for 4 more weeks.
Who Did They Recruit To Do This Study?
To do this study, the researchers recruited 17 Japanese men who were all ex-smokers, diagnosed with ACO, and with a smoking history of 66.6 ± 39.5 packs per year. The ages of participants ranged from 54-87 years old. All of the participants had mild and stable ACO. They all had episodic respiratory symptoms, increased airflow variability, incompletely reversible airway obstruction, and post-bronchodilator.
What Measurements Did They Conduct?
The researchers took measurements at 0, 4, and 8 weeks post-randomization. They used a spirometer to take various measures of respiratory function such as their vital capacity (VC), their forced vital capacity (FVC), how much air they could blow out after 1 second (FEV1), and various measurements of the speed of their airflow. Along with measuring their respiratory function, they also measured their respiratory impedance, or how hard it was for them to breathe. Measurements of their fractional exhaled nitric oxide (FeNO) were taken as an indirect measurement of their airway inflammation. To determine if there were any changes in their subjective symptom burden, the researchers also gave the participants both COPD and asthma questionnaires. The researchers also used an electrocardiogram to measure the participants’ heart rate and they did blood tests to measure their peripheral eosinophil and immunoglobulin E levels.
Take a look at this YouTube video below to watch a patient take spirometry test and to learn the steps involved!
Definitions
- Open-Label Study: A study in which both the patient and the researcher were aware of the medications the patient was taking when they were taking them (NCI Dictionary of Cancer Terms).
- Crossover Study: A study in which each participant eventually receives all of the different treatments being studied, but are given one treatment to try during a certain time period and are then “crossed over” to a different treatment during the next time period. The order in which the participants receive the treatments is determined by randomization (NCI Dictionary of Cancer Terms).
What Did They Find?
Our primary paper showed that following the use of umeclidinium (UMEC) once-daily added to fluticasone furoate/vilanterol (FF/VI) showed a significant difference in the spirometry parameters. Amongst those parameters were the COPD assessment test (CAT) and asthma control test (ACT) which are useful in quantifying the COPD symptoms in participants. CAT is comprised of 8 questions scored on a 0 to 5 scale, with a maximum possible score of 40 (score of 1-10 is mild, 11-20 is moderate, 21-30 is severe, and 31-40 is extremely severe health status impairment) (Gregoriano, 2018). The ACT score is from 1 to 5 with lower overall scores representing poor asthma control (Gregoriano, 2018). The use of COPD and ACT scores to quantify patient symptoms is common when researching respiratory disorders. However, they seem to only show adequate scores when the sample size is large enough to show a significant result. For example, a study by Gregoriano C., et al on the use and inhalation technique in patients with asthma and COPD, used approximately 165 participants with asthma and COPD which contributed to the significant CAT score difference between their controls and experimental group (Gregoriano C., 2018). The findings in both articles were similar in that triple therapy had a significant impact on COPD symptoms compared to dual therapy.
| Run-in | FF/VI | FF/VI/UMEC | p-value | |
|---|---|---|---|---|
| Spirometry parameters | ||||
| VC (as % predicted) | 82.8 (12.1) | 86.4 (12.5) | 91.8 (14.9) | < 0.01 |
| FVC (as % predicted) | 81.5 (15.2) | 84.4 (15.9) | 89.2 (16.1) | < 0.01 |
| FEV1 (as % predicted) | 46.8 (12.8) | 49.3 (14.0) | 54.4 (13.7) | < 0.01 |
| FEV1/FVC (%) | 46.2 (10.9) | 49.3 (14.0) | 54.4 (13.6) | < 0.01 |
| PEF (as % predicted) | 45.1 (16.1) | 46.4 (15.5) | 52.8 (15.5) | < 0.01 |
| FEF25–75% (as% predicted) | 14.6 (5.6) | 15.7 (7.9) | 17.8 (7.4) | 0.09 |
| MEF50 (as % predicted) | 16.4 (7.2) | 17.4 (9.5) | 20.4 (10.0) | < 0.05 |
| MEF25 (as % predicted) | 14.6 (5.6) | 15.7 (7.9) | 17.8 (7.4) | 0.09 |
| COPD Assessment Test (CAT) score | 15.1 (6.1) | 13.8 (7.3) | 13.4 (6.1) | 0.18 |
| Asthma Control Test (ACT) score | 22.5 (7.0) | 22.1 (5.4) | 22.9 (7.5) | 0.78 |
| Fres (Hz) | 17.0 (4.7) | 15.6 (5.7) | 13.0 (5.8) | < 0.01 |
Table 1. spirometry parameters after each treatment. Data retrieved from DOI: 10.5414/CP203382
The changes in the forced vital capacity as a percentage of the predicted values (seen in table 2) and the forced expiratory volume in 1 second as a percentage of the predicted value quantifying the severity of COPD. Authors mention that COPD respiratory symptoms would be measured by looking at forced expiratory volume in 1 second divided by forced vital capacity and if that value is less than 70%, the individual is categorized as having some form of COPD. The authors highlighted the fact that the mean values of resonant frequency during inspiration (Fres) were significantly lower when triple therapy was used, compared to the run-in group. Fres measures how synchronized our heart rate is with our breathing, which helps decrease the sympathetic nervous system response.
Key Takeaways
- Triple Therapy has been proven to be effective in reducing COPD symptoms in some studies; however, the number of participants in the sample is critical in order to yield adequate results.
- Further studies are required to understand the effects of triple therapy on APO
- Triple therapy is believed to improve lung function, improve respiratory symptoms, and reduce respiratory exacerbations
- The majority of spirometry parameters were higher after using umeclidinium (UMEC) and fluticasone furoate/vilanterol (FF/VI)
- Treatment options show potential as a regular treatment for ACO with no apparent sign of negative symptoms.
References:
NCI Dictionary of Cancer Terms. 2 Feb. 2011, https://www.cancer.gov/publications/dictionaries/cancer-terms/def/open-label-study.
NCI Dictionary of Cancer Terms. 2 Feb. 2011, https://www.cancer.gov/publications/dictionaries/cancer-terms/def/crossover-study.
Figure 6: “Study Design” Created Using Biorender.com
Gregoriano C., et al. (2018). Use and inhalation technique of inhaled medication in patients with asthma and COPD: data from a randomized controlled trial. Respir Res. 10:237. DOI: 10.1186/s12931-018-0936-3
Lipson D., et al. (2018). Once-daily single-inhaler triple versus dual therapy in patients with COPD. N Engl J Med. 378(18):1671-1680. DOI: 10.1056/NEJMoa1713901