Trelegy Ellipta: Is There Any Downside To Taking All Three Medications Together?

Is There Any Downside to Taking Trelegy Ellipta?

Dear Dr. Mahler:

I read your recent post and have heard of Ellipta, though now Trelegy may be one step newer…
Is there any downside to taking all these helpers at once?
I was thinking, although it is more to do in a day, that keeping them separate might be a good thing.  More effect from each on their own?
Maybe not!

Katherine from Greensboro, NC

Dear Katherine:

Thanks for commenting on my recent post about a new 3-in-1 approved inhaler by the Food and Drug Administration (FDA) for those with COPD on September 18.

Please note that this single inhaler contains three different medications for treatment of those with COPD. These medications are already combined together and are available. These are Anoro Ellipta (different bronchodilators – vilanterol and umeclidinium) and Breo Ellipta (a bronchodilator – vilanterol – and an inhaled corticosteroid – fluticasone). So, the pharmaceutical company, GlaxoSmithKline, combined all three medications together in a dry powder inhaler called Trelegy Ellipta. They performed various studies (called randomized clinical trials) as required by the Food and Drug Administration. The company then submitted the results to the FDA for review and consideration of approval.

Although it may seem confusing, the different Ellipta inhalers along with numerous other inhalers developed by other pharmaceutical companies provide many options for health care providers to hopefully make it easier for you to breathe with activities and to reduce the chances of having a flare-up (called exacerbation). These treatment strategies are provided by the a group of experts in COPD called the GOLD committee.

You asked about a downside to taking all three medications together. Please note that current recommendations for the use of inhaled corticosteroids in treating those with COPD is for those individuals who have had 2 flare-ups (exacerbations) in the past one year OR one flare-up that was “bad enough” to require hospitalization. The reason for this recommendation is that inhaled corticosteroids can have side effects. The most concerning is an increased risk of pneumonia. Other possible side effects include a yeast infection in the throat, bruising of the skin, and thinning of the bones (called osteoporosis).

As with all medications, your health care provider should consider the likely benefits of the medications along with possible side effects. Some people call this “weighing the balance.”

A scale to weigh the benefits and risks of Trelegy Ellipta

A scale represents weighing the benefits and risks of a medication


I hope that this information is helpful. I encourage you to discuss the available inhalers with your health care professional.

Best wishes,

Donald A. Mahler, M.D.

What is Triple Therapy? My Doctor has Mentioned This to Me

Triple Therapy: What Is It? What are the Benefits?

Dear Dr. Mahler:

I am curious about “triple therapy.” My doctor suggested this to me at my last visit, but said that he wanted to read more about the results of studies.

 My doctor has told me that my COPD is severe. Last winter I had a flare-up and had to be hospitalized.  I am doing fine now, taking Spiriva HandiHaler and Serevent Diskus. What are your thoughts?

Jeff from Wilmington, NY 

Dear Jeff,

“Triple therapy” refers to three different inhaled medications to treat COPD. Two are bronchodilators, and the other is an inhaled corticosteroid.

You state that you are currently taking a long-acting beta agonist – Serevent Diskus – twice a day – and a long-acting muscarinic antagonist – Spiriva HandiHaler – once a day in the morning. These dry powder bronchodilators act in different ways to open the breathing tubes by relaxing the muscle that wraps around the airways.

Serevent is one component of triple therapy

Serevent Diskus dry powder inhaler

Spiriva is one component of triple therapy

Spiriva HandiHaler dry powder inhaler







Inhaled corticosteroids are a different type of medication used to treat COPD. It is anti-inflammatory – that means it reduces redness and swelling inside of the breathing tubes.

At the present time, two different inhalers need to be used to provide “triple therapy.” According to an international group of experts in COPD called GOLD, triple therapy should be used in those patients who are short of breath with walking on the level and have had 2 or more flare-ups (called exacerbations) or one requiring hospitalization in the past year.

Pharmaceutical companies are working on putting all three types of medications – beta-agonist bronchodilator, muscarinic antagonist bronchodilator, and corticosteroid – into one inhaler. This is also called “closed triple therapy” because all medication are “closed” within one device.

Currently, the Food and Drug Administration (FDA) is reviewing a proposed “closed triple therapy” inhaler for us in the US. At the present, “triple therapy” requires use of two different inhalers.

David Lipson, MD, is first author of article on Triple therapy

David A. Lipson, M.D., of Perelman School of Medicine in Philadelphia

In the August 15, 2017, issue of the American Journal of Respiratory and Critical Care Medicine (volume 196; pages 438-446), Dr. Lipson and colleagues published one of the first reports of triple therapy in one inhaler. It is called the FULFIL study. The 3-in-1 inhaler was compared with twice daily beta-agonist and inhaled corticosteroid for 24 weeks in a total of 1,810 patients with COPD. Triple therapy showed greater improvements in breathing tests and in quality of life scores along with a 35% reduction in flare-ups compared with dual therapy. The safety was similar between the two inhaled medications.

Once again, triple therapy is recommended for those who are symptomatic (short of breath walking on the level) and are at risk for a flare-up (exacerbation) based on 2 episodes in the past year or one leading to hospitalization.


Donald A. Mahler, M.D.

Does COPD Cause Pain?

Prevalence of Pain is More Common in COPD (41%) Than Healthy Subjects (29%)

Background: Pain and shortness of breath are both unpleasant experiences which affect an individual’s quality of life. In different studies, the frequency of pain ranges from 44% to 88% in those with COPD.

Study: Dr. Annemarie Lee and colleagues at the West Park Healthcare Centre in Toronto studied 64 patients with COPD referred to a pulmonary rehabilitation program and 64 healthy subjects of the same age. All answered questionnaires about pain over a one week period, including location, its frequency, and how long it lasts, as well as questionnaires about shortness of breath, quality of life, etc..

The study is published on-line in the Journal of the COPD Foundation [2017; 4(3): In press. doi:]

Results: Age range was 48 to 91 years in the COPD group and 47 to 94 in the healthy group. Those with COPD had either severe or very severe COPD based on results of breathing tests. Pain frequency was 41% of those with COPD and 29% in healthy subjects.

anatomical locations for chest and upper back pain

Chest and upper back pain are more common in those with COPD

Pain was more common in the chest and upper back areas in those with COPD compared to healthy subjects. It was described as aching (30%), tiring (17%), and penetrating (17%). The location in the chest and upper back was associated with more air in the lungs (higher total lung capacity) as measured on breathing tests.

Those with painful experiences also had more shortness of breath with activities and higher depression scores.

Locations of the chest for pain

Rib cage

Conclusions: The authors proposed that hyperinflation of the lungs (too much air trapped in the lungs) could cause stretching of the chest wall and cause strain on ligaments between ribs as well as excessive forces on the joints.

My Comments: Unfortunately, the researchers did not evaluate the cause of pain experienced by the subjects. For example, could some of those with COPD have arthritis of the spine? 

It is important to remember that there are no pain sensors in the lung itself, but rather in the lining around the lung (called the pleura) and in areas of the muscles, joints, and ligaments in the chest wall. The treatment for too much air trapped in the lungs includes bronchodilators (inhalers that open up the breathing tubes allowing more air to exit), oxygen, and exercise training.

I am Using Oxygen at Night. Do I need Oxygen when I Sleep?

Do I Still Need to Use Oxygen at Night during Sleep?

Dear Dr. Mahler:

About a year ago my primary care doctor ordered oxygen at night when I sleep. I guess that my oxygen level was low in the office, but my level was not monitored during sleep. She really didn’t explain things very clearly except that she said to use oxygen at 2 liters/minute rate.  I really can’t tell any difference using oxygen during the night or when I wake up.  Last May my husband and I went away to Maine for our anniversary and I didn’t take the oxygen concentrator with me.  I felt fine and now only use oxygen a few nights each month when I feel a little tired. What do you think? I am 73 years  and have moderate COPD according to my doctor, but never had complete breathing tests.

Silvia from Newport, RI

Dear Silvia:

Insurance companies and the Centers for Medicare and Medicaid (CMS) have specific criteria (levels) for when they will pay for oxygen for an individual.  The oxygen level is usually

Oximeter which measures the percentage of oxygen being carried by hemoglobin in the blood

Oximeter which measures the percentage of oxygen being carried by hemoglobin in the blood

determined by a device that goes on your finger called an oximeter.  This measures the percentage of oxygen carried by the protein hemoglobin found in red blood cells.  The device sends wave lengths through the finger and a sensor determines the saturation of oxygen. This is abbreviated SpO2.

Diagram of oximeter to determine whether someone requires oxygen at night

The top piece of the oximeter emits light waves that pass through through the finger. The bottom piece has a sensor. Absorption of light differs between blood loaded with oxygen and blood lacking oxygen.

You qualify for using oxygen if your SpO2 is 88% or less.  If you level was 88% or below in the office a year ago, that would qualify you for using oxygen 24/7, not just at night. Did your doctor recommend using oxygen all of the time or just to use oxygen at night?

The decision to prescribe oxygen in the office or clinic should only be considered when you are being treated with optimal medical therapy.  In brief, this means:

  1. Not smoking
  2. Use of both types of inhaled bronchodilators (called beta-agonists and muscarinic antagonists) that work by different mechanisms (ways) to relax muscle around the breathing tubes. Available long-acting dual bronchodilators include Anoro (a dry powder) and Stiolto (a mist) used once daily in the morning.
  3. In a stable condition.

Different studies show that from 27 – 70% of those with COPD with awake SpO2 90-95% may experience substantial drops in oxygen levels during sleep. However, the consequences of these drops in oxygen (called desaturation) is unclear. These drops may contribute to more awakenings (arousals) during sleep which could lead to sleep fragmentation.

I suggest that you ask your doctor to recheck your oxygen saturation in the office.  If it is 88% or less, then you should be using oxygen all of the time. If it is 89% or higher, then it would be helpful to monitor your SpO2 when you sleep at home not using oxygen. This can determine if you have frequents drops in your SpO2 and can help guide a decision on whether you do or don’t need oxygen at night during sleep.


Donald A. Mahler, M.D.

Inhaled Corticosteroids and Pneumonia

Stopping Inhaled Corticosteroids Reduces Pneumonia

Background: Inhaled corticosteroids are an inhaled form of prednisone which reduces inflammation. Inhaled corticosteorids are approved  by the US Food and Drug Administration (FDA) to treat those with COPD in combination with a long-acting beta2-agonist bronchodilator. The names of these medications are: Advair; Symbicort; and Breo.

Studies show that these medications make it easier to breathe and reduce the chances of an exacerbation (worsening of shortness of breath, increased coughing, and/or more mucus) usually due to a chest infection. However, there is an increased risk of pneumonia in those with COPD who use Advair, Symbicort, or Breo.

Study Findings: In the November 2015 issue of CHEST (volume 148; pages 1177-1183) Samy Suissa, Ph.D., and colleagues examined health insurance information in over 103,000 individuals with COPD who used inhaled corticosteroids in the Quebec province of Canada from 1990 through 2009. Some of these stopped thier use during the study period.

The main finding was that stopping inhaled corticosteroids was associated with a 37% decrease in the rate of serious pneumonia (either requiring hospitalization or death from pneumonia).

My Comments: Both you and your health care provider should consider expected benefits and possible risks of any medication that you take. The findings of this study highlight the concern of the increased risk of pneumonia in someone taking inhaled corticosteroids and shows a decreased risk when inhaled corticosteroids are stopped.

In my practice, I advise someone with COPD to stop the medication containing an inhaled corticosteroid IF he/she has had pneumonia. I caution the individual that stopping the medication may make their breathing worse, and make sure that the person is taking both classes of different bronchodilators to improve breathing.

As always, I encourage you to discuss your individual situation with you health care provider.


Highlights from European Respiratory Society Congress

September 26 – 30, 2015, in Amsterdam

One of the highlights of the International Congress was a session on improving outcomes in those with COPD. A major emphasis was on the current goals of treatment:

  1. Reduce shortness of breath – which can generally be measured in a few weeks of starting a new inhaled bronchodilator medication
  2. Reducing the risk of an exacerbation (worsening of symptoms usually due to a chest infection) – this requires at least six months to assess.
David Singh, M.D., from University of Manchester in UK

David Singh, M.D., from University of Manchester in UK

Dr. David Singh of Manchester, United Kingdom, spoke about optimizing bronchodilation (opening the airways). He quoted one study that showed that most patients with COPD were still short of breath with activities after being started on a single long-acting  bronchodilator (Primary Care Respiratory Journal, year 2011, volume 20, page 46). He then discussed the role of using two different bronchodilators in a single inhaler to get the greatest benefit. In the US, there are two approved dual bronchodilators in a single inhaler – Anoro Ellipta and Stiolto Respimat. The evidence suggests that two bronchodilator medications that work in different ways can provide better stability in keeping the breathing tubes open longer. This means that it should be easier to breathe for those with COPD and should have a better quality of life.


Dr. Marc Miravitlies of the University Hospital in Barcelona, Spain, discussed both daytime and nighttime shortness of breath (medical word is dyspnea) in those with COPD. Studies show that many

Marc Miravitlles, M.D., of University Hospital in Barcelona, Spain

Marc Miravitlles, M.D., of University Hospital in Barcelona, Spain

individuals who have COPD wake up due to breathing difficulty. Also, poor sleep is considered a risk factor for having an exacerbation (worsening of shortness of breath and/or coughing up yellow-green mucus). Bronchodilators that work throughout the night should help if the sleep problem is due to COPD, but will not help if there is another cause like sleep apnea.

Dr. Neil Barnes, Medical Head of GlaxoSmithKline pharmaceutical company, spoke about the benefits and side effects of using inhaled corticosteroids (prednisone like medication). He emphasized that inhaled corticosteroids combined with long-acting beta-agonist bronchodilator (in US: brand names are Advair, Symbicort, and Breo) are widely prescribed, but should primarily be used in those who have had two or more exacerbations (worsening of symptoms) in the past year OR one exacerbation in the past year that required treatment in the hospital. A major concern about the use of

Neil Barnes, M.D., Medical Head of GalxoSmithKline pharmaceutical company

Neil Barnes, M.D., Medical Head of GlaxoSmithKline pharmaceutical company

inhaled corticosteroids is the risk of developing pneumonia.



My Comment: Each year at medical conferences there is growing research interest in helping those with COPD. Novel therapies are being evaluated in addition to improving inhaled bronchodilators. All of us need to promote greater public awareness of COPD and encourage the National Institute of Health, various professional organizations, and pharmaceutical companies to increase research funding.

What are the stages of COPD?

Dear Dr. Mahler:

I have moderate, or Stage 2, COPD according to my doctor. However, I don’t understand what the stages mean. Will I  go on to the next stage? How many stages are there? Overall, I am doing pretty good. I am 63 years old and still work 30 hours a week at a convenience store. In the summer I work outside to keep our property in good shape and attractive. Thanks for answering this.

Leo from Bennington, VT

Dear Leo:

The stages of COPD are based on breathing tests.  FEV1, or the forced expiratory volume in one second, is how much air you can exhale (blow out) in one second. The breathing tests should be performed after inhaling a quick acting bronchodilator (albuterol. is usually used).

The forced expiratory volume in one second (FEV1) is shown in the figure.

The forced expiratory volume in one second (FEV1) is shown in the figure.


The FEV1 value is then compared with what is expected, or predicted, for your age, sex, and height. This final value is called post-bronchodilator FEV1 percent predicted. This approach has been used for a long time even though we have major discussions at medical meetings about changing from using breathing test results to using the severity of symptoms (breathing difficulty and coughing).

There are four stages of COPD shown here.

  1.     Mild                         FEV1 80 percent predicted or higher
  2.     Moderate              FEV1 50 – 79 percent predicted
  3.     Severe                    FEV1 30 – 49 percent predicted
  4.     Very severe          FEV1 below 30 percent predicted

It is important to remember that the stages are based on how your lungs are working and not on how you feel or your breathing difficulty. Your stage of COPD may actually get better if you start taking one or more inhaled bronchodilator medications. It is also possible that your COPD will remain stable and you will stay in the moderate stage for a long time. On the other hand, breathing tests may get worse in those with COPD, particularly if you continue to smoke cigarettes or inhale irritants (dust, fumes, fibers) in the air.

It is great that you are active, and I encourage you to continue to lead a healthy life style. Let me know if you have further questions.


Donald A. Mahler, M.D.



Asthma and COPD Overlap Syndrome

Hot Topic at Respiratory Meetings – Asthma and COPD Overlap

Discussions about those individuals who have features of both asthma and COPD is a “hot topic” at medical meetings. It is important to understand this overlap, or combination, because different medications are used to treat asthma and to treat COPD (see below My Comment).

In a medical article published on-line on August 20, 2015, in the journal CHEST, Dr. Cosio and colleagues from Spain identified individuals who were considered to have both asthma and COPD. This is called asthma-COPD overlap syndrome and abbreviated ACOS.

The authors studied 831 patients diagnosed as having COPD. To identify those who also had asthma, they measured improvements in breathing tests after someone inhaled albuterol (a quick acting bronchodilator) and  examined blood tests that are usually positive in those with asthma,

Main Findings: 15% of the group were considered to have both asthma and COPD (ACOS). They were predominantly male (82%) and 63% were taking an inhaled corticosteroid medicine.

Circles show overlap between asthma and COPD. COPD includes chronic bronchitis and emphysema.

Circles show overlap between asthma and COPD. COPD includes chronic bronchitis and emphysema.

My Comment: Why is this important to you? The main reason is that inhaled corticosteroid medications are used to reduce inflammation (redness and swelling) in the breathing tubes in those with asthma. Rather, different types of inhaled bronchodilators are used to treat  those with COPD. Inhaled corticosteroids should be used to treat COPD mainly for those who have experienced frequent episodes of worsening of COPD usually due to a chest infection (called an exacerbation). One concern about use of inhaled corticosteroids in the treatment of COPD is an increased risk of pneumonia.

With any medication, there needs to be consideration of expected benefit and possible risk. You may wish to discuss this topic with your healthcare provider.