Stem Cell Treatments for COPD: An Update from the American Thoracic Society

Stem Cell Treatments for COPD: What’s New

The American Thoracic Society recently published an update on stem cell treatments for those with lung disease. The report appeared in the Public Health Information Series in the journal American Journal of Respiratory and Critical Care Medicine, volume 195, pages 13-14.

Stems cells can be used for stem cell treatments

Stem cells can become any tissue in the body

What are Stem Cells? Every organ in the body has a small number of stem cells that can replace or repair damaged tissue. However, there is still a lot to learn about stem cell types and how they work. Researchers are actively working to find a way to stimulate stem cells to repair parts of the lung.

Are Stem Cell Treatments a Possibility for COPD? In theory, yes. At the present time, there are NO proven stem cell therapies for any lung disease. The best way to find whether stem cell treatments are effective and safe is by research studies.

Are There Unproven Stem Cell Treatments? Unproven means that the therapy has not been shown to work or be effective. Hundreds of clinics offer unproven treatments using stem cells in the United States and elsewhere. Typically, cells are removed from a person’s fat or bone marrow, and then the cells are given back to the person in the blood (intravenously). This approach has not been approved by the U.S. Food and Drug Administration.

Could Stem Cell Treatments be Harmful? Risks include cells sticking or clotting in the blood vessels of the lungs and cells causing abnormal growth including tumors. In addition, some clinics may not meet normal standards of sterility (preventing infection),

Are Unproven Stem Cell Treatments Covered by Health Insurance? No. Those who choose to receive such treatments have to pay all costs on their own and will not be reimbursed by insurance companies.

Summary Stem cell treatments are not approved by the U.S. Food and Drug Administration for treatment of any lung disease including COPD. The only option is to participate in a clinical research study. Information about such trials can be found on the website – www.clinicaltrials.gov.

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.

 

 

New Alpha-1 Guidelines for Testing and Treatment

Alpha-1 Guidelines Updated from 2003

The new Alpha-1 guidelines for testing and managing Alpha-1 Antitrypsin Deficiency are published in the July issue of the Chronic Obstructive Lung Diseases: Journal of the COPD Foundation. The guidelines are intended to update and simplify a 2003 document from the American Thoracic Society (ATS) and the European Respiratory Society on the diagnosis and management of Alpha-1.

Alpha-1 is an abbreviation for a genetic, or hereditary, form of emphysema. It is called Alpha-1 Antitrypsin Deficiency. The Alpha-1 protein is made in the liver, released into the blood, and travels to the lung. It protects the lung from damage due to cigarette smoking. If there is a low level in the lung and a someone smokes cigarettes, emphysema can develop at an early age or may develop at a later age in someone who has not smoked that much.

author of new Alpha-1 Guidelines

Robert Sandhaus, M.D., Ph.D.

“We believe the Summary of Recommendations of these guidelines is the most efficient tool that busy physicians have ever had to follow best practices in detection, diagnosis and treatment of Alpha-1 in adults,” said Robert Sandhaus, MD, PhD, who co-chaired the Guidelines committee. “The Alpha-1 community has long needed more accessible guidelines based on the latest scientific literature.”

 

Major Recommendation for Testing

“All individuals with COPD regardless of age or ethnicity should be tested for Alpha-1 deficiency.”

Augmentation Therapy 

Augmentation therapy builds up the Alpha-1 protein in the lung for better protection to prevent any additional damage. The Alpha-1 protein is obtained from healthy adults, concentrated, and then given through a plastic tube placed in an arm vein once a week to prevent emphysema from worsening.

My Comment: If you have COPD, make sure that you are tested for Alpha-1 deficiency.  Your health care provider can order a simple blood test to find out about this diagnosis.

Pneumonia Risk Factors in COPD: An Analysis

Pneumonia Vaccine Associated with Lower Rate of Pneumonia 

Background: Pneumonia is a seriously chest infection that can affect healthy individuals and those with COPD. If severe, it can lead to a serious illness that requires hospitalization.

Study: Dr. Kurashima and colleagues from the Saitama Cardiovascular and Respiratory Center in Japan reviewed the risk factors for pneumonia in 509 patients with COPD. The study results were published on line in the Journal of COPD.

Chronic Obstr Pulm Dis (Miami). 2016; 3(3): In press. doi: http://dx.doi.org/10.15326/jcopdf.3.3.2015.0167 – See more at: http://journal.copdfoundation.org/jcopdf/id/1114/Risk-Factors-for-Pneumonia-and-the-Effect-of-the-Pneumococcal-Vaccine-in-Patients-With-Chronic-Airflow-Obstruction#sthash.R8878z4p.dpuf

Results: Using multivariate analsyis (which means consideration of all possible factors), the authors found that a low body mass index (a measure of weight related to height), a low forced expiratory volume in one second (how much air can be exhaled in one second), history of vaccination with the 23-valent pneumococcal polysaccharide vaccine (PPV-23), and the presence of emphysema were associated with the overall frequency of pneumonia. 

Conclusions: The pneumococcal vaccine-23 was associated with a signficantly lower rate of pneumonia in those with COPD.

My Comments: Of the four factors reported in this study, you can possibly affect or change two of these: your body mass index (or body weight) and whether or not you have received the pneumococcal vaccine containing 23 strains of the bacteria called Streptococcus pneumoniae. 

A body mass index (BMI) of less than 22 means someone who is very thin. It is possible albeit challenging for some thin individuals to gain weight. However, a healthy diet of frequent small meals is the best strategy.

Finally, make sure that you have received the vaccine called PPV-23. If you are not sure, ask your health care provider.

There is a newer vaccine called PCV-13 that contains 13 different strains of the bacteria called Streptococcus pneumoniae. Please view a Real FAQs post on May 1, 2015, , on this website for more information on the PCV-13.

Emphysema on CT scan – What is my prognosis?

What is my outlook for emphysema?

Dear Dr. Mahler:

I am 43 year old female who was diagnosed with chest ct mild emphysema. 3 years ago my pft was in normal range. I have since then quit smoking and gained a lot of weight. Also, I suffer from anxiety and I am terrified I will progress to end stage. I do not have the alpha tripsan defiency. Everything I read is doom and gloom and I feel as though Im doomed. I currently use symbicort 2x a day and albuterol as needed. Any advice would be greatly appreciated.

Val from Portland, OR

Dear Val:

You have a somewhat unique situation  You have emphysema on the CT scan of your chest, but normal breathing tests (PFTs). This generally indicates that your past cigarette smoking caused damage to your air sacs (alveoli), but

Microscopic view of the air sacs (alveoli) in the top right showing emphysema (destruction and enlargement).

Microscopic view of the air sacs (alveoli) in the top right showing emphysema (destruction and enlargement).

there is no narrowing or obstruction of your breathing tubes (airways). Remember that emphysema is one of two types of COPD – the other type is chronic bronchitis (coughing up mucus most days).

CT scan shows emphysema in the left lung. Arrows show "dark" areas in periphery of the lung with no blood vessels due to emphysema.

CT scan shows emphysema in the left lung. Arrows show “dark” areas in periphery of the lung with no blood vessels due to emphysema.

You wrote that everything that you read about emphysema is “doom and gloom.”

However, that is quite unlikely in your case as you quit smoking. As long as you don’t smoke, you should not have further damage to your lungs.

It is common that many people gain weight when they quit smoking. I encourage you to start an exercise program either on your own (walking daily) or join a community health and fitness center. I don’t believe that you qualify for pulmonary rehabilitation as your breathing tests are normal.

Finally, I encourage you to think positively because your condition should not get worse as long as you don’t smoke and don’t inhale irritants in the air.

Best wishes,

Donald A. Mahler, M.D.

Stem Cell Therapy for Advanced Emphysema: Does It Work?

Here is a typical question among many that I have received about stem cell therapy to regenerate new lung tissue in emphysema.

Dear Dr. Mahler:

I hope that you can provide an update on stem cell therapy for emphysema. I am 53 years old and have been told that I have Stage 3 COPD /emphysema. Although I quit smoking and my lung doctor has me on the “best” medications, I find that I am slowly getting worse.  I attend pulmonary rehab 2-3 times a week, and have a normal weight. I want to be around to see my granddaughter get married. Is there hope?

Sally from Boulder, CO

Dear Sally,

It is good to hear that you are doing all of the “right things” for your COPD.

You and many others have asked about stem cell therapy. Certainly, it is an attractive option in theory – to regrow new lung tissue to replace damaged emphysema.

Unfortunately, stem cell therapy remains experimental at the present time for advanced COPD.

What are stem cells?  Stem cells have the potential to develop into cells that serve many different functions in the body. In addition, in many tissues they serve as a sort of internal repair system, dividing essentially without limit to replenish other cells as long as the person or animal is still alive. When a stem cell divides, each new cell has the potential either to remain a stem cell or become another type of cell with a more specialized function, such as a muscle cell, a red blood cell, or a lung cell.

Types of Stem Cells There are two types of stem cells. 1. Those that come from a human embryo – obtained by in-vitro fertilization in a laboratory. They cells can take on the function of any part of the body including cells in the lung. 2. Those that come from developed organs and tissues in the human. They are used by the body to repair and replace damaged areas.

Current Status of Research  Here is a summary of what is happening in research laboratories. Stem cell therapy has been used successfully in the treatment of blood (hematological) and orthopedic conditions. This technology will hopefully be used to advance knowledge as a potential treatment for those with advanced emphysema. The goal would  be to regrow functional lung tissue where there is currently disease or damage.

At the present time there are over 30 trials focusing on lung disease; 7 of these are in emphysema. Of the emphysema studies, only a few are taking place in academic medical centers in the US. The major challenges are: 1. finding a appropriate source of stem cells; and 2. finding the correct dose.

At Brigham and Women’s Hospital in Boston, a stem cell research program is underway. Researchers are taking a biopsy of the lung in someone with emphysema, growing these cells in a tissue culture, and then at a later time placing them back into the individual. If this approach is successful, it will likely take many years before this type of stem cell treatment is ready for use.

To summarize, current information does not support the benefits of stem cell therapy in treating those with advanced COPD. Hopefully, that will change in time.

Keep active and stay positive.

Sincerely,

Donald A. Mahler, M.D.

 

 

Can e-cigarettes Help to Quit Smoking?

Use of e-cigarettes to Quit Smoking

Dear Dr. Mahler:

My husband wants to quit smoking. He has tried just about everything, but none of them have worked for more than a week or two. Now he wants to try smoking electronic cigarettes. What do you think?  

His doctor has told him that he has early emphysema. He is fairly active in the community and works 25 hours a week at Home Depot. 

Joan from Columbus, OH

Dear Joan,

I congratulate your husband on wanting to quit smoking.  E-cigarettes are a $2.2 billion industry in the United States, and use is increasing rapidly among adults and teenagers. 4% of US adults are regular users.

Components 

Electronic cigarettes are battery-powered devices that simulate the feeling of smoking, but without tobacco. Smoking an e-cigarette is called vaping. There are four parts.  The battery powers the e-cigarette and is usually rechargeable.

Components of an e-cigarette

Components of an e-cigarette

The battery connects to atomizer which turns nicotine liquid into vapor. Next in line is the cartridge where the nicotine liquid is stored before vaporization and where new liquid is refilled. Many newer e-cigarettes combine the cartridge with the atomizer into one component. The final part is the mouthpiece or tip. This funnels vapor from the cartomizer into the vapor’s mouth. The user activates the e-cigarette by taking a puff.

There are many types of e-cigarettes as shown.

Battery charger with USB port.

Battery charger with USB port.

Hand grenade type e-cigarette

Hand grenade type e-cigarette

 

 

 

 

 

 

Quitting Smoking with e-cigarettes

There is controversy about using e-cigarettes to help people quit smoking. However, the benefits and the health risks are uncertain, and the long-term health effects are unknown. Compared to smoking tobacco, e-cigarettes are safer for both users and bystanders.There is tentative evidence that they can help people quit smoking. They have not been proven to work better than nicotine replacement products such as the patch or gum.

Woman vaping an e-cigarette.

Woman vaping an e-cigarette.

The World Health Organization takes the view that there is not enough evidence to recommend e-cigarettes for quitting smoking. In one review, there was no difference in quit smoking rates between those using e-cigarettes and those using nicotine replacement products (as examples, gum and patches).

Safety

The vapor contains flavors, propylene glycol, formaldehyde, nicotine, carcinogens, heavy metals, and other chemicals. Overall, e-cigarettes reduce exposure to carcinogens and other toxic substances compared with smoking tobacco in cigarettes. The nicotine in the vapor is associated with heart disease and potential birth defects. There is inadequate research to demonstrate that nicotine is associated with cancer in humans.

One main concern is that e-cigarettes are unregulated. There are risks from misuse or accidents such as fires by vaporizer malfunction and explosions from battery failure. A recent article in the Seattle Times described four young adults who experienced injuries to the face, hand, and arm due to exploding e-cigarettes. In October 2015, one 24 year old man lost front teeth and suffered cuts to his lips and gums due to blast injury from an explosion.

In summary, I encourage your husband to use whatever method to help him quit smoking. If he decides to use e-cigarettes, he should hopefully do this to quit smoking and then to quit using e-cigarettes. He may consider using nicotine patch or gum instead of electronic cigarettes.

Also, I encourage your husband to discuss his plans with his health care provider.

Best wishes to both of you for success in your husband quitting,

Donald A. Mahler, M.D.

Lifestyle Options to Reduce Inflammation in COPD

How to Reduce Inflammation in COPD

Dear Dr. Mahler:

I read in your book that inflammation is part of COPD.  What does that actually mean?  I am 67 years old and was diagnosed with chronic bronchitis form of COPD about 3 years ago.  I quit smoking at the time, and still work selling real estate.  If inflammation is bad, what can I do to get rid of it? Thanks.

Bill from Pensacola, FL

Dear Bill,

In Latin, inflammation means “set afire.”  It is an important part of the body’s immune system to heal an injury or fight an infection. However, if this persists and is chronic, inflammation plays a key role in various diseases – like asthma, diabetes, heart disease, bowel disease – in addition to COPD.

woman holding candle

Smoking cigarettes and inhaling irritants causes injury to the breathing tubes and air sacs.  In response, the body calls in, or recruits, white blood cells to the area of injury.  This results in redness and swelling of the area – the features of inflammation.  See the figure on the right below.

Right photo shows acute bronchitis with inflammation

Photo on right shows acute bronchitis with yellow mucus inside the airway along with redness and swelling of the wall.

If someone continues to smoke, the inflammation persists and becomes chronic. This causes swelling in the lining of the breathing tubes that narrows the opening and reduces the ability to exhale air. In addition, inflammation makes it more likely that the muscle that wraps around the breathing tubes will constrict or tighten. This is called bronchoconstriction and further reduces the flow of air out of the lungs.

Here is what you can do to try to reduce inflammatory changes in your lungs:

  1. Don’t smoke.  It is great that you already quit.
  2. Avoid inhaling irritants in the air like smog, dust, smoke, fumes, fibers, soot, etc.
  3. Eat healthy foods that includes lots of fruits, vegetables, whole grains,
    Salmon

    Salmon

    beans, nuts, olive oil, and fish especially salmon –  that have anti-inflammatory effects.  Blueberries are the BEST.

  4. Consider spices – such as ginger root, cinnamon, clove, black pepper, and tumeric – which may provide anti-inflammatory benefits. More research is needed to know whether these and other spices help with inflammation in COPD.
  5. Get enough sleep. Studies show that when healthy individuals are sleep deprived, there is an increase of inflammation in the body. How this happens is unclear.
  6. Try to exercise at least 3 – 4 times a week.k13084522
  7. For a treat, eat dark chocolate which is loaded with organic compounds that are biologically active and function as antioxidants. These include polyphenols, flavanols, and catechins.

 

I hope that this information answers your question.

Best wishes,

Donald A. Mahler, M.D.

 

Measuring Collateral Ventilation for Bronchoscopic Volume Reduction

Dear Dr. Mahler:

I read your post on December 11, 2015, about the need to measure collateral ventilation to know who might benefit from placing valves into the airways to collapse parts of emphysema lung. My pulmonary doctor has mentioned a study/program in Boston that I am considering.  I have “advanced emphysema” and am limited in doing anything more than daily activities.  I struggle with yard work, raking, and even walking our dog. I would like to know more about how is collateral ventilation measured?  Is this complicated?

Many thanks.

Albert in Saco, ME

Dear Albert:

Your question is quite important. Studies have shown that the valves are effective in collapsing lung that is not working only if there is no collateral ventilation present. Please review information about collateral ventilation on my December 11 post.

To answer your question, there are several ways to measure whether someone has collateral ventilation. If a valve is placed in a lobe in the lung with collateral ventilation, the lobe will not collapse and therefore will not help you breathe easier. In the article by Kloosters and colleagues published in the New England Journal of Medicine, the authors used a method called the Chartis System. This system was developed by Pulmonx, a company who makes the Zephyr valves used in the study.

Here is a brief summary. I will try to make this complicated process as simple as possible.

First, you are given medication to make you sleepy and temporarily forgetful

Bronchoscopy used to measure collateral ventilation

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

(called conscious sedation). Then, a bronchoscope is passed through your nose or mouth into the breathing tubes (airways). A plastic tube is then passed through the scope, and a balloon at the end of the plastic tube is inflated to block flow or air to the “target’ lobe.

The tip of the plastic tube extends beyond the balloon and can measure any air flow to determine whether collateral ventilation is present or not (see figure below).

System used to measure collateral ventilation

Scope on right with plastic tube and balloon inflated that blocks flow of air into the lobe.

You can find more information on the website:    https://pulmonx.com/ous/products/chartis-system/

Placement of valves into emphysema lobes has been approved in most counties in western Europe and is a common treatment for advanced emphysema in Europe. However, in the US, the Food and Drug Administration has not approved this procedure at the present time. So, you will need to go to a medical center doing a study on placement of valves for emphysema. Beth Isreal-Deaconess Medical Center in Boston is the nearest center to Saco, Maine, doing this research procedure. Certainly, your pulmonary physician can refer you for evaluation if you are interested.

Best wishes,

Donald A. Mahler, M.D.

How Should I use an Oximeter?

Dear Dr. Mahler:

One of my children recently bought an oximeter for me to check my oxygen level? However, I am not exactly sure how to use this information. My doctor has told me that I have severe COPD with emphysema, but I do not use oxygen. I take Tudorza and Symbicort both twice a day and ProAir as needed. I usually get a chest cold in the winter and then take prednisone and a Z-pak.  I keep fairly active at the senior center and participate in their exercise programs usually twice a week. 

Barbara from Clearwater, FL

Dear Barbara,

An oximeter is a medical device that measures oxygen saturation. This is often abbreviated SpO2 where S = saturation; p = pulse; and O2 = oxygen.

The device passes two waves of light through the finger to measure the percentage of hemoglobin, the protein in the red blood cell, that carries oxygen. Most devices also measure heart rate.

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

 

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.

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.

What do the numbers mean? A normal value is 95% or higher. A value of 90% or higher is considered adequate or acceptable. A value of 88% or below is considered low and qualifies for oxygen use.

Are there any limitations? Yes, there are a few to know about. First, you must have good blood flow to the finger for the oximeter to be accurate. Poor blood flow can occur if your hand is cold or if you are moving a lot, like shivering. If you measure the oxygen level when walking, make sure to keep your finger/hand steady to get an accurate recording. Also, an irregular heart rhythm can affect the accuracy. Those who have atrial fibrillation (a fib) have an irregular heart beat and the values can change based on how much blood reaches the finger.

I find that some patients in my practice are overly dependent on knowing their SpO2. It is useful as a guide as how the lungs are working, but does not indicate how you are feeling or how good or bad is your breathing. Certainly, it is reasonable to check the level particularly if you are having a “bad breathing day.”

Finally, you are fortunate that one (or more) of your children is interested in your COPD and wants to help out. Make sure that you share this response with your family to help them understand what the SpO2 means.

Best wishes,

Donald A. Mahler, M.D.

 

Valves for Emphysema

New Study on Endobronchial Valves as Treatment for Emphysema

The results of a new study evaluating placement of valves inside the lung – called bronchoscopic lung volume reduction – was published in the December 10, 2015, issue of the New England Journal of Medicine.

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

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

Background: With bronchoscopic lung volume reduction, valves are placed into the breathing tubes to block the flow of air out of the specific area of the lung. This collapses part of the “bad” lung which is not functioning and allows the “good lung” to expand.  This allows the diaphragm (the main breathing muscle) to work more effectively. Ideally, this will improve lung function and make it easier to breathe.  A diagram of how bronchoscopy is done is shown on the left below; a view of one of the valves used in the study is shown on the right below.

Zephyr valve used in the study

Zephyr valve used in the study

 

 

 

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

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

 

 

 

 

 

 

 

 

Unfortunately, this procedure does not work for everyone who has emphysema. Researchers around the world are trying to find out the best candidates for this treatment. One reason that bronchoscopic lung volume reduction may not work is if someone has a hole or defect in the fissure that separates lobes in the lung. A brief anatomy lesson will help to explain this concern. There are 3 lobes or discrete parts in the right lung and 2 lobes or discrete parts in the left lung. In the figure below, fissures are shown by black curves.

Diagram showing 3 lobes in the right Lung and 2 lobes in the Left Lung. The black curves are fissures which separate the lobes. If there is a defect in a fissure, putting in a valve into one breathing tube will not collapse the desired part of the lung.

Diagram showing 3 lobes in the right Lung and 2 lobes in the Left Lung. The black curves are fissures which separate the lobes. If there is a defect or hole in a fissure, putting in a valve into one breathing tube will not collapse the desired part of the lung.

 

In some individuals, small openings or pores allow air to flow across the fissure from one lobe to another. This flow is called collateral ventilation.  However, this is not beneficial if the goal is to collapse a part of “bad” lung. The collateral ventilation allows air to bypass the lung blocked by the valves, just like a bypass road allows you to drive around or bypass a city.

Study: Klooster and colleagues at the University Medical Center in Groningen, Netherlands, were able to measure whether someone had collateral ventilation or not. In those who did not have collateral ventilation, 34 patients received endobronchial valves and 34 patients were the control group and treated with standard medical therapy.

Findings at 6 months: There were significant increases in breathing tests [by 140 ml in how much air can be exhaled in one second (FEV1) and by 347 ml in vital capacity (FVC)] and in the distance walked in 6 minutes (by 74 meters) in the valve group compared with the control group.  There were 23 serious adverse events in the valve group and 5 in the control group. One person who received valves died. Some individuals required removal of the valves (15%) or replacement of the valves (12%).

My Comment: These findings make sense. If you are going to have valves placed inside of your breathing tubes to collapse areas damaged by emphysema, the treatment team should make sure that you do not have collateral ventilation. This should lead to better overall benefits of bronchoscopic lung volume reduction.

Although the authors had patients report on their quality of life, I am disappointed that the researchers did not have the participants rate their shortness of breath with a valid questionnaire. Those with emphysema are bothered most by their breathing difficulty, and being able to breathe easier is one of the key goals of treatment.

Like another study that I summarized in September 2015 under COPD News, there are risks with the procedure and you need to weigh possible benefits and possible risks. Certainly, you should discuss these with you doctor and the specialists who perform this procedure.

 

 

Use of Valves To Treat Advanced Emphysema

Valve Study Shows Some Benefits and Some Risks

Over the past year, I have been asked by a few patients with COPD in my practice, “What else can you do to help my breathing get better?” Each of these individuals is taking available long-acting inhaled bronchodilators, is participating in pulmonary rehabilitation program, and is on oxygen.

In response to the question, I describe the possibility of a research study where a doctor passes a flexible scope thru the mouth and then into the breathing tubes to look inside the lungs (called bronchoscopy).

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

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

Umbrella-like valves are attached to the end of the scope and then placed into the breathing tubes to collapse part of the lung which is not functioning.This allows the “good lung” to expand and allows the diaphragm (the main breathing muscle) to work more effectively. Ideally, this will improve lung function and make it easier to breathe.  The procedure is called bronchoscopic lung volume reduction.

 

Photo of umbrella device taken from inside a breathing tube. The umbrella will block air from entering the lung leading to collapse.

Photo of umbrella device taken from inside a breathing tube. The umbrella will block air from entering the lung leading to collapse.

 

View of umbrella valves positioned into breathing tubes that block entry of air and collapse the lung

View of umbrella valves positioned into breathing tubes that block entry of air and collapse the lung

 

 

 

 

 

 

 

 

In the United States, this procedure is considered investigational which means additional studies are required to evaluate benefits and risks before approval by the Food and Drug Administration.

In June 2015, Dr. Davey and her colleagues published the results of a study (in the journal  Lancet, volume 386) involving 50 patients with severe emphysema. In Group 1 (25 patients), valves were placed by a bronchoscope (a scope passed thru mouth into breathing tubes) to cause collapse of one lobe of the lung. Group 2 (25 patients) was considered as a control group as individuals had the same bronchoscope passed into the breathing tubes to mimic the first group, but no valves were place (sham or fake).

The study was performed at the Royal Brompton and Imperial College in London, United Kingdom, a leading respiratory research institute. The study was not sponsored by a commercial company.

The study had several very specific requirements for individuals to enter the study:

  1. general emphysema with a lobe in one lung as a target to collapse (we all have 3 lobes in the right lung and 2 lobes in the left lung)
  2. an intact interlobar fissure on CT scan of the chest (this means that air should not be able to pass from an open lobe to the collapsed lobe after the valve has been placed)
  3. the key breathing test result – forced expiratory volume in one second (FEV1) – less than 50% of predicted
  4. low exercise capacity (unable to walk more than 450 meters (492 yards) in six minutes
  5. the need to stop because of shortness of breath after walking 100 yards or after a few minutes on the level

RESULTS at 3 months after procedure: 

Outcome                                                   Group 1          Group 2 (control group)        Signficant

Change in FEV1                                      + 8.8%                       + 2.9%                                      Yes

Change in 6 min walk                           + 27 yards                + 3 yards                                  Yes

Change in exercise time on cycle      + 25 sec                    – 11 sec                                     Yes

Quality of life                                           – 4.4 units                – 3.6 units                                No

(the lower the score the better quality of life)

RISKS: Two patients in Group 1 died within 90 days of the procedure. One patient in Group 2 was too sick to return for follow-up testing.  Two patients in Group 1 had a pneumothorax (air in the space around the lung due to rupture) which occurred at 3 days and at 12 days after the procedure). Both patients who had a pneumothorax needed a tube placed between the ribs in order to remove the air and allow the hole to heal. Four patients coughed out a valve before 3 months.

MY COMMENT: As often seen in studies, some individuals improved a lot after the procedure while others did not improve at all. Any treatment including placement of valves into the lung requires the individual to consider both benefits and possible risks. In the northeast, the closest research site in the study is Beth Isreal-Deaconess Medical Center in Boston.

 

Stem Cell Therapy

Dear Dr. Mahler:

I have been reading that stem cell treatment can repair the damage in my lungs caused by emphysema. What are your thoughts on this? I am 69 year old, and have been told that my COPD is stage 4. I use three different inhalers and oxygen at a setting of 2 when I do things, but not at rest.  I am starting to feel desperate about my breathing. Thanks. 

Catherine from Reno, NV

Dear Catherine:

Your question is quite interesting, and a few patients in my practice have asked me the same thing. I will try to explain what are stem cells without being too technical.

Stem cells are unique because they can develop into any type of tissue in the human body.

 

Stems cells can be used for stem cell therapy

Stem cells can become any tissue in the body

As they have regenerative properties, stem cells offer hope for curing a variety of diseases including emphysema and scarring in the lung (fibrosis). There are two types of stem cells – one is called embryonic because they are found in embryos and the other is called adult because they are found in the umbilical cord, placenta, blood, bone marrow, skin, and other tissues. Large numbers of stem cells are needed to repair damaged tissue.

Embryonic stem cells used for stem cell therapy

At top, embryonic stem cell colonies. At bottom, nerve cells.
.

Embryonic stem cells are grown in a culture medium where they divide and multiply. However, adult stem cells have difficulty dividing once they are removed from the human body.  Currently, scientists are trying to find better ways to grow adult stem cells in cell culture and to manipulate them into specific types of cells that have the ability to treat injury and disease.

For stem cell therapy to be useful to treat COPD, millions of stem cells are needed to be implanted into a specific part of the body, such as the lungs. To make millions of cells, a process called manipulation is required. However, the Food and Drug Administration considers that manipulation of these cells is equivalent to a prescription medication, and therefore the process must be carefully regulated.

Without going into detail, there are potential risks of stem cell therapy that need further study.

In summary, the use of stem cells for treating COPD has great appeal. However, there is very little known about short and long term effects. At the present, there are a few approved clinical trials (studies) in the United States and Canada evaluating stem cell therapy. They can be found on the website of the National Institutes of Health at www.clinicaltrials.gov.

Because of potential for harm, the lack of any proven benefits so far, and the high fees that are typically charged, I advise caution before further consideration of stem cell therapy for your COPD. Hopefully, the medical profession will learn more about this unique treatment.

Regarding your breathing, are you under the care of a pulmonary specialist? If not, I encourage to ask your doctor to refer you a pulmonologist to make sure that you are receiving optimal medical care for your COPD.

Sincerely,

Donald A. Mahler, M.D.

Will Lung Volume Reduction Surgery Help Me?

Dear Dr. Mahler:

I have been reading about lung volume reduction clinical trials. Is this procedure for people with emphysema that is diffuse?
Thank you.

Karen from Cranston, Rhode Island

Dear Karen:

Lung volume reduction surgery (abbreviated LVRS) is an operation to remove about 20 – 30% of damaged lung for those with severe emphysema. By removing some areas of the lung that are not working normally, the remaining lung can expand and be more efficient. The operation is performed either by a large incision in the chest (called thoracotomy) or by several small incisions using a scope to do the surgery (called video-assisted thorascopic surgery and abbreviated VATS).

The evaluation process is extensive to determine whether you are a “good candidate” for LVRS. It includes a medical history and physical examination, tests of how your heart and lungs function, an exercise test, and a CT scan of your chest. In one study, it was shown that those with the emphysema mainly in the upper parts of the lung and with low exercise tolerance benefited the most by having less breathing difficulty, a better quality of life, and improved ability to exercise after LVRS. You will be expected to join a pulmonary rehabilitation program for 6 – 8 weeks before surgery so that you are in the best possible shape. The surgeon will review with you the risks with this operation.

Karen, by your question it sounds like you were told that you have diffuse emphysema on a CT scan. This means that the damage is throughout your lungs rather than predominantly in the upper lungs as is preferred for best results with LVRS. If this is the case, you may wish to consider another approach IF you continue to have breathing difficulty despite being treated with the best available medications for COPD and having completed pulmonary rehabilitation program.

At certain medical centers, small devices such as coils or umbrellas are placed through a bronchoscope (small flexible tube) into an airway (breathing tube) that leads to an emphysema area. The purpose of the coil or umbrella is to collapse damaged lung so that the remaining lung can expand and function more normally. The procedure is called bronchoscopic lung volume reduction. At the present time, the placement of coil or umbrella devices has not been approved by the Food and Drug Administration (FDA) and is therefore investigational. This means you would need to be part of a study to evaluate the benefits and risks of placement of a coil or umbrella into your airway.

Photo of umbrella device taken from inside a breathing tube.  The umbrella will block air from entering the lung leading to collapse.

Photo of umbrella device taken from inside a breathing tube. The umbrella will block air from entering the lung leading to collapse.


View of umbrella devices positioned into breathing tubes that block entry of air into the lung tissue.

View of umbrella devices positioned into breathing tubes that block entry of air into the lung tissue.

I practice in New Hampshire and have referred interested patients with advanced emphysema to Dr. Adnan Majid, Director of the Emphysema Clinic at Beth Isreal Deaconess Medical Center in Boston, Massachusetts. Dr. Mahid and his team are participating in different FDA-approved clinical trials to learn about the benefits and safety of bronchoscopic lung volume reduction with the Nitinol coil (called the RENEW study) and the IBV umbrella valve (called the EMPROVE study). If you are interested, you should discuss this with your doctor, and possibly ask her/him to refer you to this medical center as it is close to where you live in Rhode Island.

What are Chronic Bronchitis and Emphysema?

Dear Dr. Mahler:

I was recently diagnosed as having COPD by my primary care doctor. She mentioned both chronic bronchitis and emphysema, but I didn’t quite understand what she meant by these terms. Can you explain?

Jack from Tacoma, WA

Dear Jack,

I assume that you had breathing tests (called pulmonary function tests) in order for your doctor to diagnose COPD. COPD consists of two types: chronic bronchitis and emphysema. The figure below shows that the breathing tubes (airways) divide many times and end in air sacs (alveoli).

The breathing tubes (bronchus) divide many times and end in air sacs (alveoli).

The breathing tubes (bronchus) divide many times and end in air sacs (alveoli).

If inhaling cigarette smoke and other irritants mainly damages your breathing tubes, then the airways become red and swell (inflammation) and glands that line the inner lining of the tubes produce a thick substance called mucus. It is usually white or gray in color. Most people with this condition cough up mucus most days, especially in the morning. This is called chronic bronchitis. It is diagnosed if you report coughing up mucus most days for three months over a two year period. A cough productive of mucus is a common complaint or symptom.

Views of the inside of a normal breathing tube on left and of chronic bronchitis on the right. Note the white-yellow mucus lining the inside of the airway in chronic bronchitis.

Views of the inside of a normal breathing tube on left and of chronic bronchitis on the right. Note the white-yellow mucus lining the inside of the airway in chronic bronchitis.

If inhaling cigarette smoke and other irritants mainly damages your air sacs (alveoli), these areas are destroyed. This is called emphysema. It is usually diagnosed by a specific type of breathing test called diffusing capacity. In emphysema, the diffusing capacity is lower than normal. Emphysema can also be diagnosed if you have a CT scan of the chest that shows typical changes. Shortness of breath with activities is the most common complaint or symptom.

Microscopic view of the air sacs (alveoli) in the top right showing emphysema (destruction and enlargement).

Microscopic view of the air sacs (alveoli) in the top right showing emphysema (destruction and enlargement).

It is possible that you have a combination of both chronic bronchitis and emphysema which is quite common.

At the present time, treatments for COPD are the same whether you have chronic bronchitis or emphysema.

I suggest that you ask your doctor the same question that you asked me for more specific information about your condition.

Sincerely,

Donald A. Mahler, M.D.