Tiotropium Slows Worsening (Decline in Lung Function) in Early COPD

Tiotropium Slows Worsening (Progression) in Those with Early COPD

Background: Tiotropium (brand name: Spiriva) is a once daily long-acting inhaled bronchodilator that has been approved for treatment of COPD for over 10 years. Studies show that it opens the airways to make it easier to breathe, reduces air trapped in the lungs, and improves both quality of life and ability to exercise.

Spiriva HandiHaler - tiotropium slows worsening of COPD

Spiriva HandiHaler dry powder inhaler

 

However, no bronchodilator has been shown to slow the expected worsening (progression) in breathing tests over time.

Study: Dr. Zhou and other investigators in China compared the changes in breathing tests of Spiriva HandiHaler and a placebo (inactive medication) over 2 years in those with “early-stage” COPD. The authors proposed that regular use of this bronchodilator would slow the expected decline in lung function as measured by expiratory volume in one second (FEV1).

FEV1 is used to grade COPD severity and assess COPD prognosis

Diagram of spirometry to diagnose COPD. FEV1 is the amount of air exhaled in one second.

Only patients with “early-stage” COPD were studied with FEV1 of 50% or higher of the predicted value. The study was conducted in 24 centers in mainland China between October 2011 and September 2015. The findings were reported in the September 7, 2017, issue of the New England Journal of Medicine, volume 377; pages 923-936.

Results: 841 patients completed the trial: 388 received tiotropium and 383 received placebo. Average age was 64 years, and 85% were men. Most patients did not complain of any shortness of breath.

The annual decline in FEV1 was significantly less in those treated with tiotropium compared with placebo when breathing tests were performed after inhaling albuterol in the pulmonary function laboratory at 2 years. The difference between treatments was 22 milliliters per year.

Conclusions: The authors concluded that tiotropium slows worsening in those with early-stage COPD as measured by post-bronchodilator FEV1.

My Comments: The current recommendations for prescribing one or two long-acting bronchodilators is to reduce symptoms and to reduce the risk of a flare-up (exacerbation) in those with COPD. However,this study challenges that approach by showing that early treatment slows progression of COPD as measured by breathing tests.

An editorial in the September 7 issue of the New England Journal of Medicine by Drs. Ko and Wong from the Chinese University of Hong Kong suggested it is likely that other long-acting bronchodilators would provide a similar benefit.

In caring for those with COPD in my practice, I have observed that many individuals have stable breathing tests when tested over several years. I believe that this stability is likely due to two factors: 1. regular use of long-acting bronchodilators; and 2. avoiding a COPD flare-up (exacerbation).

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.

Endobronchial Valve Therapy for Diffuse Emphysema

Benefits of Endobronchial Valve Therapy: Results of the IMPACT Study

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

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

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

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

Endobronchial valve used in the study

Zephyr endobronchial valve used in the study

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

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

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

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

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

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

Pneumothorax in right lung. Black arrow shows collapsed lung.

Pneumothorax in right lung. Black arrow shows collapsed lung.

Diagram of pneumothorax in left lung

Diagram of pneumothorax in left lung

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

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

Vitamins C and E and Risk of COPD

Benefits of Vitamins C and E on COPD Risk and Lung Function in Men

Study: Joshi and colleagues reported on the effects of vitamins on the risk of developing COPD and changes in lung function in those living in South Korea. The results were published in the October 2015 issue of the International Journal of COPD (volume 10; pages 2159 – 2168).

The analysis included 6,781 individuals considered “at risk” for developing COPD as well as 325 individuals with COPD. Diet was estimated from a questionnaire on food intake. The overall analysis included consideration of age, sex, married or single, income, history of asthma, and smoking.

Results: The risk of “getting” COPD was related to age, low education, low income, low weight, and cigarette smoking. However, the risk of COPD decreased with the increase of taking vitamins C and E, mainly in men. In addition, breathing tests (lung function) were improved with greater intake of vitamins C and E.

oranges - good source of vitamin C

oranges – good source of vitamin C

My Comment: This study suggests that men with COPD may benefit by taking vitamins C and E. Both vitamin C and E are antioxidants -which reduce break down (destruction) of cells in the body and are considered to fight aging (anti-aging). Good sources of vitamin C are citrus fruits (especially oranges), sweet peppers, broccoli, and soybeans; good sources of vitamin E are nuts, fortified cereals, and sweet potatoes.

Caution:  Too much vitamin E may increase the risk of prostate cancer and stroke.

What needs to be done? To further examine the benefits of vitamins C and E, it will be important to do an intervention study. This means that some individuals would either eat foods rich in these vitamins or else take vitamin pills while other individuals would follow their normal diet. However, it is unlikely such a study will be done because of expense and long-term follow-up required.

As always, you may wish to discuss these findings with your health care provider.

COPD Prognosis: Will My COPD get Worse?

COPD Prognosis: What Will Happen Over Time?

Dear Dr. Mahler:

I recently asked my doctor about my COPD prognosis.  His answer was that, “COPD is a progressive disease.” I am 63 years old, and was diagnosed about 5 years ago. I am doing pretty good at the present time, and want to be able to continue my activities as long as possible. However, I am worried that everything will slowly get worse and that I will need oxygen to get around. What are your thoughts?

Sam from Hilton Head, SC

Dear Sam:

The current definition by the GOLD committee states that COPD is “usually progressive.” The word usually was added a few years ago based on new information about the course of COPD as assessed by results of breathing tests (pulmonary function tests) over 3 – 4 years in those with moderate, severe, and very severe COPD.

The usual way to evaluate COPD prognosis (Is it getting worse?) is to consider how much air you can blow out (exhale) in one second. This is called FEV1 (see diagram below). One thing to remember is that lung function (FEV1) slowly declines in healthy people because we are getting older. This is due to loss of some of the elastic fibers in the lung tissue.

FEV1 is used to grade COPD severity and assess COPD prognosis

Diagram of spirometry to diagnose COPD. FEV1 is the amount of air exhaled in one second.

A few years ago, two different studies reported FEV1 results in longitudinal studies (those with COPD could continue their usual COPD medications). Both studies found that some individuals with COPD had stable FEV1 values over time, while another group of individuals with COPD showed that FEV1 became lower or worse.

A recent study published by Dr. Lange and colleagues in the July 9, 2015, issue of the New England Journal of Medicine sheds further light on your question. The researchers analyzed three different studies that measured FEV1 for decades. They found that one group who developed COPD started with low values for FEV1 in early adulthood and showed a normal decline in FEV1 due to aging. This means that a low value for FEV1 in early adulthood may be an important starting point for some individuals with COPD and that their lung condition may not worsen any more than what occurs with getting older.

How will you know this? Certainly, we can’t go back and know what you breathing tests were when you were 25 years old. But, we can follow the results of your breathing tests every 6 – 12 months to observe whether the FEV1 is stable, slowly declining as expected with age, or actually declining faster than expected due to COPD. You can ask your doctor about any changes in your FEV1 over the past few years.

Remember Sam, the most important thing that you can do to protect your lungs and keep them healthy is to not smoke and to avoid inhaling irritants (fumes, dust, fibers, etc.) in the air.

Finally, no one has a crystal ball to predict the future. It is important to stay active, eat healthy, maintain a normal body weight, avoid too much stress, and sleep 7 – 8 hours each night.

Sincerely,

Donald A. Mahler, M.D.

 

Stopping Smoking – Will My COPD Go from Moderate to Mild?

Stopping Smoking Will Reduce Inflammation

Dear Dr. Mahler:
 
Is it possible after stopping smoking and following doctors orders to go from moderate to mild copd in a year? Is it detrimental to a copd patient to live in a basement apartment- 5 steps down? The  furnace is not in the apartment. 
 
Thanks.
 
Ken from Richmond, VA 
 
 Dear Ken:
 Yes, if you stop smoking, the inflammation in your breathing tubes (airways) will be reduced and your lung function (results of breathing tests) will improve. How much is hard to say. Also, it is likely that your breathing tubes will produce less mucus because the irritation from smoking cigarettes will have stopped.
Reminder for Stopping Smoking

Reminder for Stopping Smoking

The categories of mild (FEV1 > 80% predicted) and moderate (FEV1 50 – 80% predicted) COPD are based on specific values on breathing tests.  If you have stopped smoking, I congratulate you and encourage you not to smoke again.  If you are still smoking, it is important that you stop completely to prevent worsening (progression) of your COPD.
I am not aware that living in a basement apartment is bad for your breathing. Certainly, you want to breathe as much fresh air as possible.
Sincerely,
Donald A. Mahler, M.D.