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.

Sincerely,

Donald A. Mahler, M.D.

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.

COPD in Women: Key Findings

COPD in Women Increasing More Rapidly Worldwide

Background: COPD in women receives little attention as a health issue even though more women die of COPD each year than of breast cancer and lung cancer combined. The general perception that COPD is a disease of older men is outdated. Throughout the world, COPD is increasing more rapidly in women than in men. Since 2000, more women than men in the United States die of COPD.

Dr. Jenkins has written about COPD in women

Professor Christine Jenkins

Review: Dr. Christine Jenkins of Sydney, Australia, and co-authors described the impact of female sex on COPD in a review article in the March 2017 issue of Chest, volume 151; pages 686-696.

Key Findings about COPD in Women: 1. For the same amount of smoking or exposure to irritants in the air, women are more susceptible to developing COPD. 2. The reasons for smoking may differ between sexes. Dr. Jenkins proposed that female empowerment through tobacco smoking and weight control are likely two reasons that women smoke. 3. Women with COPD are generally younger, smoke less, and have a lower body weight for their height than men. 4. Women tend to have more shortness of breath than men for the same level of breathing tests results. 5. In a 3-year study in the US, it was found that women had more frequent flare-ups (exacerbations) of COPD than men.

Female with COPD

How Does COPD Affect Women? In many studies it was noted that women have poorer health status and quality of life compared with men. Women with COPD report higher levels of anxiety and depression than men with COPD which adds to the burden of the disease in women.

Treating Women with COPD: Smoking cessation is an important treatment for anyone with COPD. However, women may be less successful with long-term smoking cessation than men, especially with nicotine replacement therapy. Current evidence shows that inhaled bronchodilators work the same in women as in men.

COPD in Women

Summary: The authors concluded that it is important to raise awareness of COPD in women and to develop new strategies to prevent the disease.  They also emphasized the need for educational programs for women with COPD and their families to manage their disease better.

My Comments: I offer the following two general impressions based on my pulmonary practice, although I have no explanation for these observations. 1. Women with COPD seem more motivated to “get better” and use prescribed inhalers as recommended. 2. Women are more likely than men to actually participate in pulmonary rehabilitation programs.

 

Maintenance Pulmonary Rehabilitation in COPD is Beneficial for Two Years

Maintenance Pulmonary Rehabilitation Increases Walking Distance

Background: Whether maintenance pulmonary rehabilitation programs help to sustain the short-term benefits is unclear.

Study: Researchers in Spain studied patients with COPD over 3 years after they completed a standard 8-week pulmonary rehabilitation program. Subjects were randomized (divided by chance) into two groups: those who received maintenance therapy and those in a control group (no maintenance).

Cycle ergometer for maintenance pulmonary rehabilitation

Cycle ergometer

What was the maintenance program?  Patients exercised at home three times a week doing: 15 minutes of chest physiotherapy; 30 minutes of lifting weights (which were bought by patients); and 30 minutes of riding a stationary cycle (provided by the hospitals). A physiotherapist called the patients every 15 days; during the alternate week, patients went to the hospital for a supervised training session.

Patients assigned to maintenance pulmonary rehabilitation did arm training with weights

Woman with COPD doing arm curls with hand weights.

What did the control group do? Patients in the control group were advised to exercise at home without any supervision. They were encouraged to walk or buy a stationary cycle for home use.

The study results were published in the March 1, 2017, issue of the American Journal of Respiratory and Critical Care Medicine (pages 622-629).

Results: For the total of 138 patients, average age was 64 years, and the amount of air exhaled in one second (FEV1) was 34% predicted. There were 68 patients in the treatment group, and 70 in the control group. More than 50% of those who started the study failed to complete the 3 years. Main reasons for stopping were a COPD flare-up (exacerbation), other medical problems (called co-morbidities), and death.

Those in the treatment group improved significantly more than the control group for: 1. distance walked in 6 minutes and 2. the BODE index [B = body mass index (weight and height); O = FEV1; D = breathlessness; E = 6-minute walking distance]. However, there were no differences in health-related quality of life between the two groups.

Conclusions:  The authors concluded that the 3-year maintenance pulmonary rehabilitation program provided improvements in walking distance and the BODE index compared with usual care. These improvements lasted for 2-years; after that, there no longer was a beneficial effect.

My Comments: This study is notable because it has the longest follow-up period of any published randomized trial of maintenance pulmonary rehabilitation. The findings support the benefits of continued exercise following completion of a pulmonary rehabilitation program.

One limitation of the study is that it primarily involved men so that it cannot be assumed that women would experience the same benefits.  However, women may be more compliant than men and are likely to live longer.  

I recommend participation in pulmonary rehabilitation to all of my patients with COPD and strongly encourage maintenance after completing our 12-week program.

Endobronchial Valve Therapy for Diffuse Emphysema

Benefits of Endobronchial Valve Therapy: Results of the IMPACT Study

Reason for the Study: Placement of an endobronchial valve into the breathing tube has been shown to improve lung function and shortness of breath in those with emphysema mainly in the upper parts of the lung (called heterogenous emphysema). Whether this therapy is beneficial in those with diffuse emphysema (damage throughout the upper and lower parts of the lung) is unclear.

Study: This study was conducted in Austria, Germany, and the Netherlands. All subjects had severe emphysema with lung function [how much air was exhaled in one second (FEV1)] between 15% to 45% of the predicted value. A CT scan was performed in all subjects to assess the extent of emphysema. Only those with less than 15% difference in emphysema scores between the target lobe of the lung and the same lobe on the other lung were included.

All subjects were assigned by chance to receive placement of the Zephyr endobronchial valve (EBV) in one lobe of the lung OR usual care.

The study was reported in the November 1, 2016, issue of the American Journal of Respiratory and Critical Care Medicine, volume 194, pages 1073-1082.

Endobronchial valve used in the study

Zephyr endobronchial valve used in the study

Results: Of the 93 subjects, 50 received usual care and 43 received endobronchial valve placement. 17 subjects who were initially assigned to have a valve placed could not participate because they were found to have collateral ventilation (See post on 12/27/15 on measuring collateral ventilation and what it means).

On average, four valves were placed in each of the 43 subjects in the EBV group. After 3 months of treatment, there was improvement of 14% in FEV1 in the EBV group, while FEV1 declined by 3% in the usual care group. This 17% difference between groups was statistically significant.

Zephyr valve prevents air from entering the lung. Air can only move out of the lung, resulting in collapse of emphysema lung.

Zephyr endobronchial valve prevents air from entering the lung. Air can only move out of the lung, resulting in collapse of emphysema lung.

More subjects in the EBV group improved in walking distance for 6 minutes by 26 meters or more (50% versus 14% in usual care) and for quality of life by 4 points or greater (57% versus 25% for usual care).

Adverse Events: Over the 3 months period, 44% of the EBV group and 12% in the usual care group had serious adverse events. There were 12 pneumothoraces (air in the lining around the lung) in 11 subjects in the EBV group. All of these required the subject to be treated in the hospital with a tube placed between ribs to drain the air. In five of these subjects, one or more valves had to be removed.

Pneumothorax in right lung. Black arrow shows collapsed lung.

Pneumothorax in right lung. Black arrow shows collapsed lung.

Diagram of pneumothorax in left lung

Diagram of pneumothorax in left lung

Conclusions: Endobronchial valve therapy can provide meaningful improvements in lung function, exercise tolerance, and quality of life in those with diffuse emphysema without collateral ventilation. Some subjects experienced serious adverse events, mainly pneumothorax (see chest xray above and diagram on left). 

My Comments: Placement of endobronchial valves for those with advanced emphysema is common and considered standard of care in in many European countries. In the United States, this procedure is investigational as it has not been approved by the Food and Drug Administration. Studies are underway in the US to further evaluate endobronchial valve therapy.

Emotional Intelligence is Associated with Wellbeing and Self-Management

Emotional Intelligence Is Important in COPD

Background: Emotional intelligence is the ability to understand and manage personal thoughts and feelings. It can influence your communication with others. It is a trainable skill that has been used in corporate business to improve well-being and performance.

first author of study evaluating emotional intelligence.

Dr., Roberto Benzo of the Mayo Clinic.

Study: Dr. Roberto Benzo from the Mayo Clinic studied 310 patients with COPD who were 69 years of age on average. The key breathing test (FEV1) was 42% of the predicted value on average. All subjects answered numerous questionnaires. The study findings were published in the Annals of the American Thoracic Society in January 2016 (volume 13, pages 10-16).

Findings: Emotional intelligence was significantly and independently associated with self-management abilities, quality of life (shortness of breath, fatigue, emotions and mastery) after adjusting for age and breathing test results.

Conclusions: Dr. Benzo and his team concluded that emotional intelligence is important for those with COPD. The authors commented that attention to it may address the current gap that exists in the treatment of emotional parts of COPD which is related to decreased quality of life and increased health care use.

Store employee tying shoe of elderly shopper.

Store employee tying shoe of elderly shopper

My Comments: I congratulate Dr. Benzo and his colleagues on addressing a novel feature of COPD that has not received much attention in daily care and management efforts.

Emotional intelligence affects:

  • Performance at school or work. Emotional intelligence can help you navigate the social complexities of the workplace, lead and motivate others, and excel in your career. In fact, when it comes to gauging job candidates, many companies now view emotional intelligence as being as important as technical ability and use testing before hiring.
  • Physical health. If you’re unable to manage your emotions, you probably are not managing your stress either. This can lead to serious health problems. Uncontrolled stress can raise blood pressure, suppress the immune system, increase the risk of heart attack and stroke, contribute to infertility, and speed up the aging process. The first step to improving emotional intelligence is to learn how to relieve stress.
  • Mental health. Uncontrolled emotions and stress can also impact your mental health, making you vulnerable to anxiety and depression. If you are unable to understand, be comfortable with, and manage your emotions, you’ll be at risk of being unable to form strong relationships which can leave you feeling lonely and isolated.
  • Relationships. By understanding your emotions and how to control them, you’re better able to express how you feel and understand how others are feeling. This allows you to communicate more effectively and forge stronger relationships, both at work and in your personal life.

Acupuncture for Relief of Breathlessness

Can Acupuncture Help my Breathing?

Dear Dr. Mahler:

I want to know your thoughts on using acupuncture to help my breathing.   I was told 6 years ago that I had COPD, and my breathing continues to slowly get worse. I was taking Spiriva and Advair for years, and use ProAir several times a day. My doctor recently had me stop both Spiriva and Advair, and tried me on Anoro.  It may have helped a little, but I really can’t do the things that I want because I get winded easily. On some days, I am short of breath just getting out of bed or getting dressed. I did pulmonary rehabilitation in the past, but can’t exercise because of back pain due to spinal stenosis. I tried acupuncture a few years ago for my back pain, and it helped a lot. Do you think that it can help my breathing problem?

Betty from Red Bank, NJ

Dear Betty:

According to traditional Chinese medicine, qi is the life force that flows through pathways in our body. If there is an  imbalance between complementary forces – yin (means shady side) and yang (means sunny side) – qi is disrupted and illness develops. Acupuncture involves the placement of thin needles into the skin to correct imbalances in qi.  There are at least 350 different acupuncture points in the body where energy flow can be accessed. Generally, at each treatment, 5 – 20 needles are inserted at various acupuncture sites and left in place for 10 – 20 min. Usually, there are 6 – 12 treatments over a few months.

Multiple needles placed into skin of individual.

Multiple needles placed into skin of individual.

Acupuncture is most commonly used for pain relief, and is generally safe when done by an appropriately trained practitioner using clean technique and single-use needles.

Effects of Acupuncture in COPD

Different studies have examined the effects of acupuncture for those who have COPD. In November 2014, Coyle and colleagues from Australia reviewed the results of 16 studies which compared acupuncture with no treatment in patients with COPD (medical journal: Alternative Therapies in Health and Medicine)(http://www.ncbi.nlm.nih.gov/pubmed/25478799). Overall, patients had less breathlessness and had better quality of life after acupuncture compared with placebo (sham or pretend treatment). In a few studies, investigators measured levels of endorphins (naturally occurring narcotic substances made in our bodies), and found that they increased after acupuncture, while there was no change in these levels after placebo. It is possible that the release of endorphins (just like taking morphine) with acupuncture may have contributed to a feeling that breathing was easier and quality of life was improved.

Should You Try Acupuncture?

I suggest that you share this information  with your doctor and ask about any possible risks. Also, you will need to find out if there is a licensed acupuncturist in your area. If there is, you may wish to call her/his office and ask specifically about that person’s experience in treating those with COPD. Acupressure points for relieving breathing problems are shown below (sites A – E).

Acupressure points for relieving breathing problems.

Acupressure points for relieving breathing problems

Acupressure points for relieving breathing problems.

Acupressure points for relieving breathing problems.

Acupressure points for relieving breathing problems.

Acupressure points for relieving breathing problemPlease let me know if you try acupuncture and whether it is helpful for you.

Please let me know if you try acupuncture and if it helps you.  Best wishes,

Donald A. Mahler, M.D.