Low Handgrip Strength in COPD Associated With Flare-ups

Low Handgrip Strength Is A Marker of Frailty 

Background: Frailty occurs with aging. Two components of frailty are muscle weakness and unintentional weight loss of more than 10 pounds. Handgrip strength is a measure muscle weakness and is a strong predictor of all cause mortality in the general population.

Device to measure handgrip strength

Device to measure handgrip strength

However, the importance of strength of the hand muscles in those with COPD is unknown.

D.r Martinez is the first author of study of handgrip strength

Dr. Carlos Martinez is Assistant Professor of Medicine at the University of Michigan School of Medicine

Study: Dr. Carlos Martinez and colleagues evaluated handgrip strength in 272 patients with COPD who were participants in a study called COPDGene funded by the National Institutes of Health. Subjects recorded the number of COPD flare-ups (exacerbations) in the past year and during 2 years of follow-up. The study was published in the November 2017 issue of the Annals of the American Thoracic Society (volume 14; pages 1638-1645).

Results: Subjects: Average age was 65 years; 45% were women; and 8% were African-American. During the previous year, 31% had a flare-up.

Handgrip Strength: 65% of the subjects had low handgrip strength compared with 15% in those living in a community without COPD. It was associated with lung function (amount of air exhaled in one second – called FEV1), shortness of breath, and distance walked in six minutes (called 6 minute walk test). The authors calculated that for every 1-kilogram decrease in handgrip strength, there was a 5% higher risk of having a flare-up.

Conclusions: Low muscle strength measured by handgrip testing was associated with a higher risk of a flare-up.

My Comments: Low handgrip strength is a marker of reduced physical performance in the elderly and has been shown to be a risk factor for all-cause death as well as cardiovascular mortality.

Resistance training can increase muscle strength

Woman with COPD doing arm curls with hand weights.

These findings of the study support the need for early identification of  muscle weakness in those with COPD. In addition, the results suggest that such individuals should be participate in physical therapy and/or in pulmonary rehabilitation. Resistance training 2 -3 times a week using light weights or stretch bands can increase general muscle strength including the muscles used for hand gripping.

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.

Bronchiectasis Can Cause Frequent Flare-ups of COPD: Results of New Study

Bronchiectasis Can Cause Frequent Flare-ups: Need CT Scan of Chest for Diagnosis

Background: Bronchiectasis (pronounced bron-kee-eck-tuh-sis) is a lung condition in which the breathing tubes (airways) are damaged and widened along with inflammation and chronic bacterial infection.

bronchiectais can cause frequent flare-ups of COPD

Bronchiectasis with widening of the breathing tube (airway) and thickening of the wall.

Bronchiectasis may occur as a result of pneumonia. This can happen in otherwise healthy individuals as well as those with COPD. Those who have bronchiectais typically have a chronic cough that usually produces yellow or green mucus and are prone to recurrent chest infections.

Study: Dr. Minov and colleagues from Macedonia compared flare-ups (exacerbations) of COPD over 12 months. The study results were published in the journal Medical Sciences 2017, volume 5 (doi:10.3390/medsci5020007)

Results: Of the 54 subjects, 27 had bronchiectasis on CT scan of the chest, and 27 did not. Those with bronchiectasis had more frequent flare-ups that generally lasted longer (6.9 days compared with 5.7 days).

Conclusions: The authors concluded that bronchiectasis can cause frequent flare-ups of COPD. These episodes may last longer than in those who do not have bronchiectasis.

My Comments: With frequent flare-ups of COPD, consider

bronchiectasis can cause frequent flare-ups of COPD

Cystic changes in the lungs due to bronchiectasis.

bronchiectasis. Recurrent chest infections are common in those with bronchiectasis because bacteria live in damaged area of the lungs. Symptoms are a persistent cough that raises yellow-green mucus. Your health care provider should order a CT scan of the chest to make a diagnosis. Next, he/she should request a sample of mucus to send to the laboratory to identify a specific bacteria.  This information helps to select the best antibiotic.

Long-term antibiotic therapy is typically required to reduce the number of bacteria in the damaged breathing breathing tubes and lung tissue. All bacteria can never be totally eliminated from the lung.

In an April 2017 issue of the American Journal of Respiratory and Critical Care Medicine (volume 195, pages P15-P16), Patient Education materials address, “What is Bronchiectasis?”


Loss of Lung Function Noted with Flare-ups (Exacerbations) of COPD

Loss of Lung Function Greater in Mild COPD

Background: With a sudden flare-up of COPD, individuals have more shortness of breath, coughing, and/or wheezing. These are called an exacerbation. Studies show that flare-ups are associated with worse health status and are associated with increased risk of dying. However, it is unknown whether flare-ups cause more loss of lung function than expected with just getting older.

Study: The COPDGene study enrolled over 10,000 individuals who were current or former smokers with and without COPD. This report describes the first 2,000 patients with COPD who returned for a follow-up visit 5 years later. During the study, flare-ups were recorded by patients every 6 months.  The study was published in the February 1, 2017, issue of the American Journal of Respiratory and Critical Care Medicine (volume 195; pages 324-330).

Results: More than 1/3 of subjects (37%) had a flare-up during the 5 years. These flare-ups were associated with greater excess decline (worsening) in the amount of air exhaled in one second (FEV1) in all stages (1, 2, and 3) of COPD.  This excess decline was greatest in those with mild COPD where each flare-up was associated with an additional 23 milliliters per year decline in FEV1. If the flare-up was severe and required the person to be hospitalized, there was an even greater decline in FEV1 of 87 milliliters per year.

Dr. Dransfield is first author of the article that describes loss of lung function with acute exacerbations of COPD.

Dr. Mark T. Dransfield, Professor of Medicine at the University of Alabama at Birmingham.

Conclusions: Dr. Dransfield and colleagues concluded that sudden flare-ups are associated with greater declines (worsening) of lung function in those with COPD, especially with mild disease. In contrast, there was no worsening of lung function when current and former smokers without COPD had similar respiratory infections.

My Comments: It is well known that flare-ups due to chest infections result in inflammation (redness and swelling) in the breathing tubes (airways).  This can cause narrowing of the breathing tubes and plays a role in the decline in how the lungs work.

Also, these findings raise the possibility that preventing flare-ups (exacerbations) could prevent worsening of lung function, and thereby slow or prevent progression of the disease. Treatment with medications may need to be considered in those with mild-moderate COPD and not wait until the condition is more severe. 

You may wish to discuss how you can reduce the risk of a flare-up with your health care professional.

Frequent Exacerbations of COPD and Bronchiectasis on CT Scan

Why Am I Having Frequent Exacerbations?

Dear Dr. Mahler:

I recently had a CT scan without contrast which shows no increase in several bullae, but now shows bronchiectasis.  My doctor said this was common with copd (emphysema FEV1 = 26% predicted), but not what classification. 

I have never had a cough or sputum even with exacerbations, which I have every 4 – 6 weeks for 3 years.  Should I ask for further clarification of this?  My doctor prescribed azithromycin every other day, but after several weeks always get diarrhea.  Thank you for your input.

Marie from Saco, ME

Dear Marie,

It sounds like your doctor ordered the CT scan of your chest to look for a reason for your frequent exacerbations. As I sure that you know, it is unusual to have flare-ups every 4 – 6 weeks as you are experiencing. It is important to figure out the reason.

On October 28, 2016, I posted the findings presented at the 2016 CHEST meeting that bronchiectasis was a risk factor for frequent exacerbations. If you have not read it, I encourage you to review the information (under the heading COPD News).

Bronchiectasis is a chronic condition in which the walls of the breathing tubes are thickened from long-term inflammation and scarring. It usually develops as a result of pneumonia which can damage the lungs and provide a reservoir, or space, for bacteria or mycobacteria. Over time, the number of bacteria increase in number leading to symptoms such as cough, yellow-green mucus, chest congestion, and difficulty breathing.

CT scan shows cystic bronchiectasis which can cause frequent exacerbations

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.

Bronchiectasis is common in those with COPD. In one study, bronchiectasis was found in 29% of 110 patients from 40 – 80 years old who were diagnosed as having COPD by their primary care physician (O’Brien. Thorax. year 2000; volume 55; pages 635-642).

Even though you are not coughing up any phlegm, I suggest that you ask your doctor to see if it possible to try to obtain a sample of mucus from your lungs. The reason is to find out if you have a chronic lung infection that is causing repeated exacerbations. The sample should be sent to the microbiology laboratory at the hospital for culture of bacteria, mycobacteria, and fungi.

The easiest approach is to breathe a solution of saline (salt water) from a nebulizer to see if this can cause you to cough something up. A respiratory therapist can help with this.

If this is not successful, you may want to ask your doctor about

Diagram of scope passed thru mouth into the lungs (called bronchoscopy)

Diagram of scope passed thru mouth into the lungs (called bronchoscopy)

bronchoscopy. This is an out-patient procedure in which a tube is placed through your mouth and then passed into the breathing tubes. Sterile water can be passed through a channel in the scope; the water can “capture” possible infectious organisms. The fluid is then suctioned back into a container for culture. I have done this in some individuals to successfully identify whether a bacteria, mycobacteria, or fungus is contributing to repeated flare-ups.

Finally, have you been tested for alpha-1 antitrypsin deficiency? Bronchiectasis is common in those with this hereditary type of emphysema. A simple blood test is used to test for this condition.

Also, I suggest that your doctor consider measuring immunoglobulin levels (A, G, and M) in your blood to evaluate for acquired immunodeficiency. Immunoglobulins are proteins in the blood that fight infection. Low levels may make it more likely for infections to occur. Replacement therapy is available for low Immunoglobulin G (abbreviated IgG) levels which can help the body fight or prevent infections.

Best wishes on finding an answer.

Donald A. Mahler, M.D.



For COPD Flare-ups: Stop Smoking, Pulmonary Rehab, and Medications

Preventing COPD Flare-ups or Exacerbations 

In the April 2015 issue of the journal CHEST (volume 147; pages 883-893), Criner and co-authors summarize available treatments that can help to reduce the chances of a COPD flare-up, also called an exacebation.

Dr. Criner wrote about preventing COPD flare-ups

Gerald Criner, M.D., Chair and Professor, Thoracic Medicine and Surgery at Temple University

The authors divided the types of treatment into three categories. These recommendations are based on studies for preventing a flare-up (exacerbation), but these treatments may also improve shortness of breath and quality of life.

Non-pharmacologic and vaccinations 

  1. flu vaccine
  2. stop smoking (counseling and treatments)
  3. pulmonary rehabilitation if the flare-up was within the past 4 weeks
  4. case management with direct access to a health care specialist at least monthly
  5. education about flare-ups with a written action plan and case management

 Inhaled medications (both beta-agonist and muscarinic antagonists are types of bronchodilators)

  1. long-acting beta-agonist
  2. long-acting muscarinic antagonist
  3. short-acting beta-agonist plus a short-acting muscarinic antagonist
  4. inhaled corticosteroid and long-acting beta-agonist combination
  5. long-acting beta-agonist and long-acting muscarinic antagonist

Oral medications

  1. long-term macrolide antibiotic (dose and duration of treatment are unknown)
  2. roflumilast (for those with chronic bronchitis form of COPD and a history of at least one flare-up in the previous year)
  3. theophylline
  4. N-acetylcysteine

If you have recently experienced one or more COPD flare-ups, you may wish to ask your doctor about these treatments to help reduce the chances of having another flare-up. For the inhaled medications, the different generic types are listed with the understanding that there are many specific brand names.