Combination Bronchodilators – An Analysis of Benefits

Combination Bronchodilators Improve Lung Function, Quality of Life, and Shortness of Breath

Background: There are two different types of bronchodilators (inhaled medications) that relax the muscle that wraps around the breathing tubes to allow more air to go in and out of the lungs. One type is called a beta2-agonist, and the other type is called a muscarinic antagonist.

Respiratory system - shows where combination bronchodilators work to open airways

Most of the 23 branches (divisions) of breathing tubes have muscle that wraps around the outside.

Why is This Is Important for You to Know? Because these two types of bronchodilators work in different ways to open breathing tubes. In the US, there are currently 4 available combinations of these two types of bronchodilators in a single inhaler device. In alphabetical order, the brand names are: Anoro; Bevespi; Stiolto; and Utibron.

Study: Because these combination bronchodilators are relatively new, Dr. Oba and colleagues at the University of Missouri School of Medicine reviewed 23 different studies that compared combination bronchodilators with one bronchodilators (called monotherapy). The analysis was published in the journal Thorax; year 2016; volume 71; pages 15-25.

Results: A total of 27,172 patients with COPD were included in the analysis. The combination bronchodilators had significantly greater improvements in breathing tests, quality of life score, and shortness of breath with daily activities compared with just one bronchodilator. In addition, there were fewer moderate-to-severe flare-ups (called exacerbations) with combination therapies compared with long-acting beta2 bronchodilators, but not compared with long-acting muscarinic antagonists.

Finally, there were no differences in safety with combination bronchodilators compared with a single medication.

Conclusions: Combination therapy was most effective in improving breathing tests, ability to breathe easier with daily activities, and overall quality of life. Safety was similar between combinations and monotherapy.

Like lollipops, combnation bronchodilators are better than one

Child holding two lollipops

My Comments: These findings support the simple observation that 2 is better than 1 with most things in life, including bronchodilators. Certainly, most children would rather have two lollipops than just one. The same concept applies to combination bronchodilators for those with COPD. Make sure to ask your health care professional whether you would benefit from combination therapy.

Dry Powder Inhalers: You Need to Breathe In “Hard and Fast”to Get the Powder Deep into the Lungs

Dry Powder Inhalers Have Internal Resistances

Background: Inhaled bronchodilators are the cornerstone for treatment of those with COPD. However, it is important that the person be able to inhale the medication deep into the lungs in order to open the airways and make it easier to breathe.

Of the four different inhaling devices for bronchodilators, the most common is called the pressured metered-dose inhaler shown in the figure below. Simply pressing the canister down releases a spray (aerosol) from the mouthpiece.

Example of metered-dose inhaler. This is a different system than dry powder inhalers.

Pressurized metered-dose inhaler.

Many bronchodilators are available in dry powder inhalers (see below). All dry powder devices have an internal resistance. As a result, you need to inhale “hard and fast” to literally pull the powder out of the device and inhale it deep into the lungs.

Different dry powder inhalers

Dry powder inhalers have an internal resistance.

There is a simple breathing test to determine if you have enough inspiratory force to inhale the powder successfully out of the inhaler. This test is called peak inspiratory flow rate (abbreviated PIFR). Here is a picture of the In-Check DIAL used to measure PIFR.

In-Check DIAL to measure the resistance of dry powder inhalers

In-Check DIAL to measure peak inspiratory flow rate

Study: Dr. Loh and colleagues at the Winston-Salem Baptist Medical Center in North Carolina measured PIFR in patients just before discharge from the hospital for a flare-up (exacerbation) of COPD. The study results are published on-line in the Annals of the American Thoracic Society on April 13 (doi: 10.1513/AnnalsATS.201611-903OC).

Results: 52% of the 123 subjects had a PIFR below 60 liters/min. A value of 60 or higher is considered “optimal” to inhale the powder deep into the lungs.   Those with PIFR less than 60 liters/min were more likely to be readmitted to the hospital over 90 days for another COPD flare-up (28%) compared with subjects who had PIFR at least 60 or higher (14%).

Conclusions: The authors concluded that a low PIFR is common in those admitted to the hospital for a COPD flare-up. They recommended that the medical team measure PIFR before discharge, especially if a dry powder is being prescribed.

My Comments: With a PIFR of less than 60, it more likely that some or most of the powder stays in the mouth and throat. IF you are taking a dry powder bronchodilator and IF you find that it does not help you breathe easier, then you should ask your health care provider to measure your PIFR. If an In-Check DIAL is not available to test your PIFR, then you should ask about a different delivery system – possibilities include a pressurized metered-dose inhaler, a soft mist inhaler, or a nebulizer.

Woman inhaling aerosol from nebulizer

Soft mist inhaler

Breathe Easier with Two Bronchodilators: Less Shortness of Breath and Less Albuterol Use

Breathe Easier with Two Bronchodilators

Background: About 90% of patients with COPD are still short of breath with activities if using a single long-acting bronchodilator (either a beta-agonist or a muscarinic antagonist). In such situations, the 2017 GOLD statement recommends use of a combination of both classes of bronchodilators to achieve the best effects (see my post under the heading COPD News on December 3, 2016). Thus, the experts on the GOLD committee agree that you should be able to breathe easier with two bronchodilators. 

Study: Dr. Edward Kerwin and co-authors who work at GlaxoSmithKline pharmaceutical company studied a total of 494 patients with COPD who reported that they experienced at least some shortness of breath despite taking a long-acting bronchodilator tiotropium (brand name: Spiriva) in the HandiHaler device for at least three months. Patients were assigned by chance to either continue Spiriva HandiHaler OR to use a combination of

Anoro Ellipta enables patients to breathe easier with two bronchodilators

Anoro Ellipta contains two different bronchodilaors

two bronchodilators (brand name: Anoro Ellipta). The study results were published in the International Journal of COPD, 2017, volume 12, pages 745-755.

Results: Compared with a single bronchodilator (brand name, Spiriva HandiHaler), there were significantly greater improvements in breathing tests (lung function), the need to use albuterol as a rescue inhaler, and in shortness of breathe with activities of daily living. There were no differences is side effects between treatments.

Conclusions: Two different classes of bronchodilators provide greater benefits, including being able to breathe easier, than one bronchodilator.

My Comments: The results of this study are consistent with several other trials showing quite simply that “two is better than one” in most things in life including inhaled bronchodilators.

Bevespi contains two different bronchodilators in a single device

Bevespi Aerosphere contains two different bronchodilators

At the present time there are three available “two in one” bronchodilator inhalers – brand names are Anoro, Stiolto, and Bevespi. A fourth one called Utibron should become available in the near future.

Stiolto Respimat contains two different bronchodilators

If you are taking a single inhaled bronchodilator and have shortness of breath, I suggest that you ask your health care professional whether a trial of a “combination bronchodilator” is reasonable. At least one of these options should be covered by most health insurance policies.