COPD Flare-ups: Not Everyone Recovers

Consequences Of COPD Flare-ups: Some Improve, Others Do Not   

Background: COPD flare-ups are worsening of symptoms and are usually due to a chest infection (bronchitis or pneumonia) or inhaling something bad (like an irritant) in the air. The medical word for a COPD flare-up is an exacerbation.

Previous studies have shown that recovery for COPD flare-ups is quite variable. Some individuals are back to normal in a few weeks, while others seem to never get back to their baseline.

Study: Drs. Murray and Leidy who work at Evidera (a company that provides consulting and research services) analyzed the results of two 12-week studies evaluating a new medication (called a neutrophil elastase inhibitor) for those with COPD. All subjects completed a daily electronic dairy each evening for 2 weeks before being started on a medication or placebo and then for 12 more weeks. The 14 items in the dairy is called EXACT.

Changes in the daily EXACT score were used to measure Recovery or Worsening compared with values before starting the medication. In some subjects, there was not enough time to assess recovery or worsening because the flare-up occurred close to the end of the study. These were called “Censored” by the authors and were not analyzed.

The study was published in the February 2018 issue of the Journal of the COPD Foundation (volume 5, pages 27-37). doi:

Results: Of the 1,346 subjects, 31% had a flare-up during the 12 week period. 260 subjects recovered, while 80 experienced persistent worsening.

Recovery and persistent worsening in the those with COPD flare-ups

EXACT scores in those with a COPD flare-up at 0 days. This is noted by the two peaks. Those who recovered are noted by the solid line. Those who had persistent worsening are shown by the dashed line above the solid line.

Both groups were similar at the start of the study. The persistent worsening group had more breathlessness and chest symptoms compared with the recovery group.

Conclusions: The authors concluded that some patients have difficulty recovering from COPD flare-ups leading to worse health status and shortness of breath without any change in breathing tests (lung function).

My Comments: In my practice it is common to see individuals for are frustrated with shortness of breath and/or cough that persist after a chest infection or flare-up.

It is important to figure out why this happens. 1. In some, there may be persistent inflammation in the lungs, and then a course of prednisone should be prescribed. 2. In others, there may be weakness and deconditioning (“out of shape”) because of prolonged inactivity during the illness. For this problem, starting or re-starting an exercise program is crucial. The best approach is with a pulmonary rehabilitation program. 3. Another possible reason is psychological as anxiety or depression can make everything seem much worse. For this problem, referral to a psychologist or counselor should be considered along with possible medications for either anxiety or depression. 4. It is also important to make sure that the cause for breathing difficulty is not due to another medical problem such as a heart condition. Appropriate testing is the first step to evaluate for this possibility.

Asthma and Emphysema: What is the Best Treatment If I Have Glaucoma??

Asthma and Emphysema: Concerns of Treatment with Glaucoma 

Dear Dr. Mahler:

What is a good medication to treat someone with ASTHMA/Centrilobular Emphysema who also has closed angle glaucoma?

Darlene from Tulsa, OK

Dear Darlene:

Both asthma and emphysema (a type of COPD) are diseases of the lung. In asthma, the primary problem is inflammation and narrowing in the breathing tubes (airways), while in emphysema the primary problem is damage/destruction of the air sacs (alveoli). In someone who had both asthma and COPD, the condition is called asthma-COPD overlap. The figure shown below illustrates the overlap between asthma and COPD (chronic bronchitis and emphysema).

Diagram shows overlap between asthma and emphysema

Diagram shows overlap between asthma and COPD (chronic bronchitis and emphysema)

It is estimated that about 25% of those with COPD have features of asthma. In general, those with both features of asthma and COPD have worse symptoms (cough and/of shortness of breath), poorer quality of life, and an increased risk of flare-ups (exacerbations) compared to those with COPD alone.

Treatment for Both Asthma and Emphysema

First, it is important that you not smoke and avoid all irritants in the air, such as dust, fumes, particles, smog, etc. Inhalers are used to treat the inflammation of asthma and bronchodilators to open the breathing tubes for both asthma and emphysema. Use of one or more inhaled medications depends to a great extent on how severe are your symptoms and whether you have had frequent flare-ups. Typically, “triple therapy” is used that includes an inhaled corticosteroid and both types of long-acting bronchodilators – beta-agonists and muscarinic antagonists.

Types of Glaucoma

You mentioned that you have “closed angle glaucoma.” As you know, glaucoma is an increase in pressure in the eye. There are two major types of glaucoma – open angle and closed or narrow angle.

In a healthy eye, excess fluid leaves the eye through the drainage angle, keeping pressure stable.

In a healthy eye, excess fluid leaves the eye through the drainage angle, keeping pressure stable.

Open angle is the most common (90%) type and typically occurs after age 50. Closed angle is usually hereditary and affects those who are far-sighted (trouble seeing near).

The prescribing information for the muscarinic antagonist bronchodilators (brand names are Atrovent, Combivent, Incruse, Seebri, Spiriva, and Turdoza) states that these medications “should be used with caution in patients with narrow angle glaucoma.” A safe approach is for you to use a combination of a beta-agonist and inhaled corticosteroid. There are different combination inhalers  (brand names are Advair, Breo, Dulera, and Symbicort) approved for treatment of asthma and/or COPD

Darlene – If these medications do not control your breathing symptoms, then you should ask your eye doctor (ophthamologist) whether a muscarinic antagonist can be tried safely.

Please note, the advice provided is not a substitute for asking your health care professional about your specific situation.


Donald A. Mahler, M.D.


Report Shows Reduced COPD Flare-ups With A New Treatment – Mepolizumab (Nucala)

Reduced COPD Flare-ups With New Treatment

Background: One goal of treatment for those with COPD is reduced COPD flare-ups. Based on results of studies in those with asthma, there is interest in targeting the eosinophil – a type of white blood cell that is a normal part of the body’s immune system – in COPD. Too many eosinophils may lead to redness and swelling (inflammation) in the lungs that can cause asthma and COPD breathing attacks.

Mepolizumab (Nucala) targets blood eosinophils

A microscopic view of a blood smear shows an eosinophil (an inflammatory cell) in the center surrounded by smaller red blood cells.

Up to 40% of patients with COPD have elevated levels of eosinophils in the blood. It appears that high levels of eosinophils are associated with an increased risk of COPD flare-ups (exacerbations). Inhaled corticosteroids can reduce flare-ups and are frequently prescribed along with one or two bronchodilators to reduce possible flare-ups. This is called triple therapy (see posts on September 21, 2017, and August 17, 2017).

Mepolizumab (brand name: Nucala) is a “humanized monoclonal antibody” made in hampster ovary cells that blocks interleukin-5, which regulates eosinophils.

How meoplizumab (Nucala) works

Diagram of how mepolizumab blocks interleukin-5 to reduce eosinophils – an inflammatory cell

Dr. Ian Pavord

Dr. Ian Pavord, Professor of Respiratory Medicine at the University of Oxford

Study: Dr. Pavord and colleagues reported on two studies evaluating mepolizumab (Nucala) compared with placebo (inactive) in those with COPD who had two or more flare-ups or at least one leading to hospitalization in the past year. These flare-ups occurred even though all subjects were taking inhaled “triple therapy.” Mepolizumab or placebo was given by subcutaneous shot (injection) every 4 weeks over one year. The results were compared in those with normal and with high levels of eosinophils in the blood.

The study was sponsored by the pharmaceutical company – GlaxoSmithKline. The findings were published in the September 12, 2017, issue of the New England Journal of Medicine (volume 377; pages 1613-1624).

Results: Overall, mepolizumab (100 mg dose injected every 4 weeks) reduced COPD flare-ups treated with an antibiotic and/or prednisone compared with placebo (inactive) in patients with COPD who had high levels of blood eosinophils.

Conclusion: The authors concluded that eosinophilic inflammation in the breathing tubes (airways) contribute to flare-ups (exacerbations) of COPD. By blocking interleukin-5 with mepolizumab (Nucala), there were reduced numbers of eosinophils in the blood and reduced COPD flare-ups over one year.

My Comments: Mepolizumab (Nucala) was approved by the US FDA (November 4, 2015) for the treatment of those with severe asthma who have high eosinophil counts in the blood.

If this monoclonal antibody receives approval by the Food and Drug Administration for those with COPD, it will offer a new treatment option  for those with COPD on “triple therapy ” who continue to have frequent flare-ups.

Please view my financial disclosures under the heading ABOUT.

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.

Pulmonary Embolism Can Cause A COPD Flare-up (Exacerbation)

Pulmonary Embolism Cause of 16% of Unexplained COPD Flare-ups

Background: About 70% of flare-ups of COPD (called exacerbations) are usually due to chest infections (bronchitis or pneumonia). In 30% of the time, there is no clear cause or explanation. One possibility is inhaling irritants in

Deep vein thrombosis can break off and cause pulmonary embolism

Swelling of right leg due to blood clot (called deep vein thrombosis)

the air. Another possibility is a pulmonary embolism – the medical term for a blood clot that usually starts in the legs (called deep vein thrombosis), then breaks off, and travels to the lungs. This can cause sudden shortness of breath as well as chest pain.

A blood clot in the legs can cause swelling of the leg as seen in the photo on the right. A diagram of a blood clot in a blood vessel in the leg is shown below.

Blood clot can break off and cause pulmonary embolism

Blood clot is shown above left knee.





A blood clot in the lung is typically diagnosed by a CT scan of the chest with injection of dye (contrast) into a blood vessel of the arm.

Study: Dr. Aleva and colleagues from Nijmegen, The Netherlands, performed an analysis of seven published studies examining causes of COPD flare-ups. This is called a meta-analysis. The results were published in the March 2017 issue of the journal CHEST (volume 151; pages 544-554).

Results: Of 880 patients with an unexplained flare-up of COPD, 16% were due to pulmonary embolism. In one study, those with pulmonary embolism were more likely to have chest pain when breathing in (81%) compared with those who did not have a pulmonary embolism (40%). Also, those with pulmonary embolism were less likely to have symptoms of a respiratory infection (coughing up yellow-green mucus and chest congestion).

Conclusions: Pulmonary embolism is a frequent cause of unexplained flare-ups of COPD. The authors suggest the health care providers consider this diagnosis especially when someone has chest pain and signs of heart failure and when a chest infection appears unlikely.

My Comments: If you have a flare-up of COPD and do not have an apparent chest infection, you should be aware that a blood clot in the leg may travel to the lungs and cause shortness of breath and possible chest pain. A CT scan of the chest is typically performed to look for this problem. If found, then blood thinning medication (called anti-coagulation) is required to prevent new blood clots from forming. The body will then dissolve the blood clots in the leg and chest.

Palliative Care: Increased Use for Hospitalized COPD Patients

Use of Palliative Care in COPD

Background: Palliative care focuses on providing people with relief from the symptoms, pain, physical stress, and mental stress of a serious illness.  It is provided by a team of doctors, nurses, occupational and physical therapists, and other health care professionals. It is appropriate at any age and at any stage in a serious illness.  It is not limited to only those as part of end-of-life care.  Palliative care can be provided at home, in the hospital, and in skilled nursing facilities.  

This care may be part of hospice services, but can be offered to any patient without restriction to the illness or outlook (prognosis).  For those with COPD, palliation typically focuses on relief of breathing difficulty and strategies for conserving energy.

Study: Dr. Barret Rush and colleagues at the University of British Columbia in Vanouver, Canada, recently published an analysis of the use of palliative care in the United States between 2006 to 2012. The findings were published in the January 2017 issue of the journal CHEST (volume 151; pages 41 – 46).

Results: From 2006 to 2012, the use of palliative care was 1.7% of the 181,689 patients with COPD hospitalized for a worsening of symptoms (called an exacerbation) and were also receiving oxygen at home. During this seven year period, there was a 4.5 times increase in referrals for palliative care.  In general, those referred for these services were older (75 years compared with 71 years) , had longer hospitalizations (5 days compared with 3 1/2 days), and were more likely to die in the hospital (32% compared with 2%).

Patient in the hospital receiving palliative care

Supportive care provided in the hospital

Conclusions: The use of palliative care increased dramatically during the seven year period. The barriers to receiving palliative care included race, low socioeconomic status, size of the hospital, and region of the country.

My Comments: Palliative care can provide important services for those with advanced COPD. The specialist will ask each person what are her or his major health concerns and goals. Usually, services focus on helping the individual breathe easier and on strategies for performing daily activities. In general, care referrals are greater in larger teaching hospitals. This reflects the presence of these services compared with smaller rural hospitals.

Bronchiectasis Can Cause Frequent COPD Flare-ups

Bronchiectasis Is Linked to Increased Risk of a COPD Exacerbation

Background: Bronchiectasis is a chronic condition in which the walls of the breathing tubes are thickened from long-term inflammation and scarring. Typically, bronchiectasis is a result of a pneumonia which damages parts of the lung. As a result of the damage, mucus produced by the cells lining the breathing tubes does not drain normally. Mucus build-up can lead to a chronic infection. A cycle of inflammation and infection can develop, leading to loss of lung function over time.

CT scan shows cystic bronchiectasis

A slice of the chest on a high-resolution CT scan in a 62 year old with cystic bronchiectasis. The cysts are seen on the lower portions of both lungs.

Different types of bacteria and mycobacteria can infect the damaged areas of the lung causing:

  1. chronic coughing
  2. coughing up blood
  3. shortness of breath
  4. chest pain
  5. coughing up large amounts of mucus daily
  6. weight loss
  7. fatigue
  8. thickening of the skin under the finger nails and toes (called clubbing)

Poster Presention at CHEST meeting October 25, 2016, in Los Angeles: Dr. Kosmas of the Metropolitan Hospital in Piraeus, Greece, presented findings in 855 individuals with COPD 

42% of the patients were found to have evidence of bronchiectasis on CT scan of the chest. About 20% had experienced more than one flare-up (exacerbation) of COPD in previous year. The investigators also found that the severity of COPD predicted the increased likelihood that a person would have bronchiectasis.

Dr. Kosmas commented at the poster presentation that, “Bronchiectasis is an area in the lung that is destroyed by pneumonia, and bacteria reside there. It results in a low-grade infection, and can then lead to inflammation and an exacerbation.”

My Comments: The symptoms of bronchiectasis usually start off as mild with a persistent cough that produces yellow or green mucus. An antibiotic may help to clear up the mucus, but typically the yellow or green color returns after a few weeks.

A CT scan of the chest is important to diagnose this condition. Then, a fresh sample of the mucus should be obtained to send to the laboratory to identify the specific type of infection (sputum culture). Different blood tests should also be ordered to look for possible medical conditions that may contribute to bronchiectasis (for example, cystic fibrosis, immunodeficiency, HIV infection, alpha-1 antitrypsin deficiency, rheumatoid arthritis, and inflammatory bowed disease).

If you experience frequent chest infections, or continue to cough up yellow-green mucus persistently, ask you health care provider to consider bronchiectasis.

Reduced Exacerbations with Two Bronchodilators

11% Reduced Exacerbations with Dual Bronchodilators

Dear Dr. Mahler:

I recently read about the results of the FLAME study on a COPD website.  As I understand the post, two different bronchodilators were better for reducing flare-ups of COPD than Advair.  I am 59 years old and have had COPD for four years. My doctor started me on Advair Diskus when I was diagnosed along with ProAir as needed. I have been doing pretty good, but had pneumonia this past winter. Should I ask my doctor about the two bronchodilator combination instead of taking Advair? Thanks for your advice.

Sam from Boulder, CO

Dear Sam:

The results of the FLAME study were presented at the International Conference of the American Thoracic Society in San Francisco in May 2016 and published in the New England Journal of Medicine on May 15, 2016 (doi:10:1056/NEJMoa1516385). Dr. Jadwiga Wedzicha is the first author of the study.

The FLAME study was a head-to-head comparison of: ♦ two different types of bronchodilators [indacaterol – a long-acting beta-agonist and glycopyrronium – a long-acting muscarinic antagonist] – brand name is Ultibro AND ♦ a bronchodilator [salmeterol] and an inhaled corticosteroid [fluticasone] – brand name is Advair.

3,300 patients from 43 countries participated in the study. After one year, the rate of COPD exacerbations (“flare-ups”) was 11% lower with indacaterol-glycopyrronium compared with salmeterol-fluticasone. Patients who received the two bronchodilators also had better quality of life and used albuterol as rescue medication less frequently.

Dr. Wedzicha commented that, “I think we can say that . . . a dual bronchodilator is the first choice combination that can be used in patients with COPD.”

Sam – I suggest that you discuss these findings with your doctor. You should be aware that an inhaled corticosteroid medication (such as fluticasone as found in Advair) is associated with an increased risk of pneumonia. For this reason alone, it would be reasonable to stop Advair since you had pneumonia this past winter. The reduced exacerbations (flare-ups) with indacaterol/glycopyrronium (Ultibro) is another reason to consider a dual bronchodilator inhaler. At the present, Ultibro is not available in the US.

Anoro Ellipta dry powder inhaler

Anoro Ellipta dry powder inhaler

Stiolto Respimat delivers a fine mist.

Stiolto Respimat delivers a fine mist.

However, Anoro Ellipta and Stiolto Respimat are dual bronchodilators available in the US and are similar to Ultibro used in the study. Neither of these medications contain a inhaled corticosteroid.


Once again, I encourage you to talk to your doctor about the results of the FLAME study and ask her/him about replacing Advair with one of the two combination bronchodilators.

Best wishes,

Donald A. Mahler, M.D.

Highlights 2016 American Thoracic Society Conference

American Thoracic Society Conference in San Francisco

The annual American Thoracic Society conference is one of the major respiratory meetings in the world. It was attended by over 17,000 health care workers and those working for pharmaceutical and medical device companies from 90 countries. The main focus in on research in lung disease.

Reducing exacerbations (flare-ups) of COPD was a popular topic. One reason is that hospitals are being penalized by lower payments (reimbursement) for those readmitted to the hospital within 30 days of being discharged for an exacerbation of COPD as part of the Affordable Care Act.  Thus, most hospitals and health care systems have developed programs, or pathways, to try to prevent re-admissions to the hospital.

Presentation on May 15 at the American Thoracic Society conference: Dr. Roberto Benzo from the Mayo Clinic reported on a study that

Dr., Roberto Benzo of the Mayo Clinic.

Dr., Roberto Benzo of the Mayo Clinic.

compared the use of health coaches versus usual care after discharge from the hospital after a COPD exacerbation. The goal was to provide better care and to prevent re-admissions to the hospital. There were two treatment groups of the 215 individuals hospitalized for a flare-up of their COPD.

♦ a written action plan plus weekly calls after discharge by a health coach  to check on how the person was doing

♦ usual care

The results showed a reduction in re-admission to the hospital in the group who received weekly calls up to 9 months after discharge, but not at 12 months, compared to the usual care group. Scores for breathing difficulty and fatigue were better for those who received calls from health coaches.

This study is published on-line in the American Journal of Respiratory and Critical Care Medicine.Am J Respir Crit Care Med. 2016 Mar 8. [Epub ahead of print]

Another area of interest at the meeting was the use of coils placed into the breathing tubes of those with advanced emphysema.

Presentation on May 16 at the American Thoracic Society conference: The results of the RENEW trial were presented by Dr. Frank Sciurba of the University of Pittsburg School of Medicine. All participants had

Dr. Frank Sciurba of the University of Pittsburgh School of Medicine

Dr. Frank Sciurba of the University of Pittsburgh School of Medicine

advanced emphysema with hyperinflation of the lungs (unable to exhale the normal amount of air out of the lungs). The two treatment groups were:

♦  10 – 14 Nitinol coils were placed through a tube passed into the mouth and then into breathing tubes (called bronchoscopy) into one lobe of the lung to compress or collapse parts of the lung. A second procedure was performed 4 months later into one lobe of the opposite lung (158 subjects)

♦ usual care (157 subjects)

How do the coils work? The coils compress parts of the lung that are diseased and also help to keep breathing tubes open allowing better emptying of air during exhalation.

Xray of chest that shows several coils in the left lung

Xray of chest that shows several coils in the left lung

The main outcome was how far the subjects could walk in 6 minutes at 12 months after treatment.

Results: In the coil treated group compared to usual care: there was a significant increase of an average of 14 meters (45 feet) in the walking distance and a significant improvement in quality of life by 8.9 units (a 4 unit change is considered significant).

Complications: pneumonia requiring hospitalization – 35% in the coil group vs. 19% in the usual care group; pneumothorax (air in the lining of the lung) – 10% in the coil group and 1% in the usual care group.

This study adds to our knowledge of the possible benefits and possible complications of bronchoscopic lung volume reduction for those with advanced emphysema. This study was published online in the Journal of the American Medical Association (JAMA) on May 15, 2016. doi:10.1001/jama.2016.6261



Prednisone for A Worsening (Exacerbation) of COPD

The Good and Bad of Prednisone

Dear Dr. Mahler:

My problem is that I seem to need prednisone for a long time after every cold or chest infection. I am 76 years old, have had COPD for about 3 years, and take Spiriva HandiHaler and the higher dose of Symbicort inhaler along with ProAir when needed.  Since January when I caught a chest cold, I have been on different doses most of the time. My doctor has tapered me off prednisone, but within about 3-4 days, my breathing turns bad again. Do you have any suggestions? I am concerned because I am hungry all of the time and have gained about 10 pounds since January.

Thanks for any help.

Ida from Piscataway, NJ

Dear Ida:

The body responds to any infection by calling in (recruiting) inflammation cells to fight the

A microscopic view of a blood smear shows an eosinophil (an inflammatory cell) n the center surrounded by smaller red blood cells.

A microscopic view of a blood smear shows an eosinophil (an inflammatory cell) in the center surrounded by many smaller red blood cells.

virus or bacteria. However, in a chest infection, the inflammation (appears as redness and swelling) causes the walls of the breathing tubes to thicken.  This causes narrowing of the breathing tubes (as shown on the right of the figure) making it harder to breathe.

Photo on right shows chronic bronchitis due to inflammation and there is yellow mucus inside the airway

Photo on right shows redness and swelling (inflammation) of the wall of the breathing tube. Prednisone is used to reduce inflammation for a worsening (exacerbation) of COPD.

Prednisone is frequently used to treat a chest infection that causes you to be more short of breath. It is an anti-inflammatory medication that is used to treat a lot of inflammatory conditions including a worsening of asthma and COPD. Prednisone is effective in reducing the number of eosinophils. Based on results of different studies, it is usually given at a high dose (like 40 mg) for a total of 5 days.

For unclear reasons, in some individuals the inflammation persists for weeks to months, and 5 days of treatment is not enough.  In such cases, your breathing gets worse within a few days of stopping the medication. If this is happening, you will likely need a longer course of prednisone that is tapered slowly. Because long term use may cause side  effects, you need to work closely with your health care provider to figure out the dose of prednisone and how long you will require it.

The goal should be to get you off prednisone. If this is not possible, then the goal should be the lowest dose of prednisone to allow you to breathe comfortably and function.

There are many possible side effects of prednisone.  If used short term ( a few days to a few weeks), prednisone may cause difficulty sleeping, extra energy, change in mood, a “hyper” feeling, and an increase in blood glucose (sugar).  If used long term (more than a few weeks), other problems may occur such as an increase in the risk of an infection, a feeling of fatigue, high blood pressure, weight gain, swelling of the legs, and thinning of the bones (osteoporosis). Certainly, you should discuss the benefits and possible side effects of prednisone with your health care provider.


Donald A. Mahler, M.D.


N-acetylcysteine (NAC) Reduces Exacerbations

Meta-analysis Shows Benefit of n-acetylcysteine (NAC)

Dr, Mario Cazzola and colleagues published a review of 13 studies which examined the effects of n-acetylcysteine (abbreviated NAC) in preventing COPD exacerbations. Exacerbations are worsening of COPD symptoms usually shortness of breath and cough typically due to a chest infection (acute bronchitis or pneumonia). The review was published in September 2015 issue of the European Respiratory Review (volume 24; pages 451-461).

Dr. Mario Cazzola

Dr. Mario Cazzola of the University of Rome Tor Vergata

What is NAC? It is a antioxidant that is available as a health supplement in the United States, typically in capsule form. Antioxidants are widely used to protect cells from damage induced by reactive oxygen species.

Results: Those with COPD who had chronic bronchitis (coughing up mucus most days) had significantly fewer exacerbations with NAC compared with placebo (inactive).  There was a 35% reduction in exacerbations for 635 patients based on four studies at a dose of at least 1,200 mg of NAC each day. The authors states that NAC was well tolerated.


My Comment:  This report is called a meta-analysis which means it combines all published studies on a particular topic.  Why do this?  Many individual studies may not include enough subjects to show a difference in treatment. However, a meta-analysis includes a larger group although the studies are not usually identical in design.

NAC is not a prescription medication. It is typically available at health food stores or can be ordered on line. Based on this meta-analysis, a dose of 600 mg capsules taken twice a day is recommended IF you have the chronic bronchitis type of COPD. Certainly, you should discuss the use of NAC with your health care provider before starting this supplement. There is no evidence that NAC will help those with the emphysema type of COPD.

Example of one product of n-acetylcysteine

Example of one product of n-acetylcysteine


Another NAC product

Another NAC product

NAC is also used to treat an overdose of acetaminiphen (Tylenol) and to loosen thick mucus as can occur in those with cystic fibrosis and COPD.

n-acetylcysteine, an Antioxidant, Reduces Exacerbations of COPD

Benefits of n-acetylcysteine in Reducing COPD Exacerbation

Background: An exacerbation means sudden worsening of cough and/or shortness of breath usually due to a chest infection. It can have a major impact on someone’s daily life and may be bad enough to require a visit to the doctor or Emergency Department. So, prevention of an exacerbation for someone with COPD is an important goal in the management.

Study: In this study of 120 patients performed in Hong Kong, China, the authors (Tse and colleagues) tested whether n-acetylcysteine (abbreviated NAC) might prevent exacerbations in two groups of patients with COPD: low risk – less than two exacerbations in the previous year; and high risk – 2 or more exacerbations in the previous year. Half of the patients took 600 mg of NAC twice a day, and the other half took identical placebo tablets twice a day. Neither the patients nor the doctors knew who was taking which medication for the one year period. Results were published in the September 2014 issue of CHEST (volume 146; pages 611 – 623).

Results: NAC was successful in reducing the number of exacerbations and in prolonging the time until the first exacerbation occurred only in the high risk patients (2 or more exacerbations in the previous year), but not in the low risk patients. There were no major side effects with NAC or placebo.

How does NAC work? NAC is an antioxidant that fights inflammation and thins mucus in the breathing tubes.

What do these results mean for you? You should remember that there are many things that you can do to prevent getting sick and having an exacerbation. These include:
1. get flu and pneumonia vaccines
2. avoid inhaling cigarette smoke and airborne irritants
3. use good hand hygiene by not touching your eyes, nose, and mouth with your fingers
4. stay physically active as participation in pulmonary rehabilitation reduces exacerbations
5. ask your doctor about medications approved by the Food and Drug Administration to reduce a COPD exacerbation. These include salmeterol and fluticasone propionate (Brand name: Advair); tiotropium (Brand name: Spiriva); vilanterol and fluticasone furoate (Brand name: Breo); and roflumilast (Brand name: Daliresp)

If you had 2 or more exacerbations in the previous 12 months, you are considered at high risk for having another one. I suggest that you discuss the results of this study with your health care professional to find out if he or she believes that NAC may be helpful for you. NAC does not require a prescription, and is typically available at a health food store or can be ordered on line.

One product of n-acetylcysteine

One product of n-acetylcysteine

If you take NAC, I strongly recommend the 600 mg dose twice daily as used in this study published in CHEST. You should expect that it will take several months or longer to find out if it will be helpful. However, NAC offers one more option to help prevent a COPD exacerbation.

News from The 2014 American Thoracic Society Conference

The American Thoracic Society held its International Conference from May 16-21 in San Diego, California, and was attended by approximately 15,000 professionals including pulmonary doctors and nurses, book publishers, and employees of pharmaceutical companies interested in lung diseases.

Several sessions at the conference focused on preventing COPD exacerbations. An exacerbation means an increase in coughing, more phlegm which may be yellow or green, and/or more shortness of breath usually due to a chest infection.

As part of the Affordable Care Act, hospitals will not be paid if you are readmitted to the hospital within 30 days after being discharged with a diagnosis of a COPD exacerbation. This rule starts in October 2014. One of the speakers, Gerald Criner, M.D. of Temple University School of Medicine in Philadelphia, emphasized that a follow-up appointment with your primary care or pulmonary doctor was important in preventing the need for re-hospitalization. An appointment about 2 weeks after discharge makes good medical sense as it enables your doctor to check on how you are doing and make sure that you are taking the best medications for your COPD. Your doctor can also check your oxygen level as some individuals improve enough that oxygen can be stopped if it was prescribed at the time of discharge.

It is IMPORTANT that you and family members make sure that you have a follow-up scheduled about 2 weeks after being discharged from the hospital. At that appointment, make sure to ask your primary care or pulmonary doctor about different medications that have been approved by the Food and Drug Administration to reduce the risk of having another COPD exacerbation. These include inhaled medications:

  • tiotropium (Brand name: Spiriva™ HandiHaler™)
  • fluticasone propionate and salmeterol combination (brand name: Advair™)
  • fluticasone furoate and vilanterol (brand name: Breo™ Ellipta™)
  • Your doctor may also consider prescribing roflumilast (brand name: Daliresp™), a pill taken once daily, that reduces the risk of an exacerbation, but only if you cough up phlegm most day (chronic bronchitis), have severe COPD, and have a history of frequent exacerbations.