Special report: breathing new life into COPD research

Dr John Heffner from the American Thoracic Society, about the causes and costs of chronic obstructive pulmonary disease (COPD), while Russell Bowler and Scott Van da Walker from the National Jewish Medical and Research Center talk to Leslie Knudson about the latest diagnostics for and treatment of COPD.

Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death in America. Over 11.4 million Americans have COPD while another 12 million are likely to have it and not even know; worldwide, the disease effects nearly 600 million people and accounts for more than 2.2 million deaths each year. COPD includes emphysema and chronic bronchitis and is most commonly found in people over the age of 40 who are (or were) smokers. However, environmental exposure to hazards such as, dust, chemicals or fumes in the workplace, also have a part to play in contracting COPD.

Education

Dr Heffner is a pulmonary critical care physician who also serves as President of the American Thoracic Society, a professional organization whose mission is to improve global health in the areas of respiratory medicine, clinical care medicine and sleep medicine.

The American Thoracic Society is educating the American public to make them more aware of COPD, the factors that cause it and where they can find help. The society does this in many ways, one of which is by partnering with various other organizations in the development of clinical practice guidelines to inform both patients and clinicians, as well as improving clinical outcome. “We are looking at the science of COPD guidelines, development and implementation on a global reach,” says Heffner. “For example, we are sponsoring a workshop on the ideal methodologies for developing and implanting clinical practice guidelines to promote best clinical practices around COPD care. This will be attended by all the world’s major respiratory professional societies along with the national institutes of health.” Heffner adds that the American Thoracic Society also has many members who are experts at patient education; as such, the society is able to develop patient education materials around COPD.

Causes

COPD is carried in the broad patient population. There are some patients who have alpha 1 antitrypsin deficiency, a congenital enzyme defect wherein they can develop COPD at an accelerated rate affecting them in perhaps their fifth decade of life, if not earlier. It is accelerated by smoking and the conjunct of this congenital defect and smoking is a very strong indicator of advancing into obstructing lung disease. “In the developed and developing world, smoking is the major cause of COPD, accounting for perhaps 85 percent of instances,” Heffner points out. “Smokers then develop different forms of COPD from early abnormalities that may remain relatively symptomatic for a number of years until a patient develops symptoms, at which point it may have already progressed to irreversible destruction of lung tissue.”

As well as smoking, there are other possible causes of COPD. Mainly these are to do with smoke and smoky environments and, more specifically in third world countries, homes that rely on burning wood and cow dung for heat, energy and cooking. Young children and adults inhaling this type of material may be at more risk of developing COPD.

Heffner has been a big advocate of clamping down on such causes, calling for more stringent standards on fine particulate matter pollution. Asked why he feels so strongly about this he answers: “We feel strongly because evidence does exist that fine particulates do increase mortality from many different directions. We know that they can be cancer causing, the lung can be a portal for entrance into the body – fine particles can make it down into the lower reaches of the lung and then transmit into the bloodstream and then be deposited in the coronary arteries. These fine particles can be associated with cardiac mortality and we feel that the evidence does require a very stringent prohibition as to the significance of these fine particles.” Heffner goes on to say that the American Thoracic Society research recognizes that fine particles are a degree higher than nano-particles, and there is increasing awareness that nano-particles are similarly picked up by cells in the airway and deposited and distributed in ways that we are yet to discover or understand. However, it is understood that these nano-particles may have a serious consequence to health.

Possible prevention

It is important to have early detection systems in place and individuals should remove the removable risk factors, such as smoking or exposure to biomass fuels. In third world countries there is major interest in educating the governments that other sources of fuel are necessary. “Part of our treatment is prevention and a part of that is the launch of non-smoking campaigns where we have had some success in decreasing smoker rates,” says Heffner. “However, the tobacco industry has increased their marketing focuses in third world nation where smoking rates are on the rise.”

Costs

Healthcare costs associated with COPD are expected to be about $800 billion over the next 20 years. Heffner thinks this is an entirely realistic figure, “With the aging population and the onset of COPD in a symptomatic phase later in life, we are yet to see a downward turn of the epidemic of chronic pulmonary disease in the mortality and morbidity of COPD. This is in contrast to other conditions such as, heart disease, stroke and other vascular disorders. In the United States we will see a growth of the economic burden of COPD, but clearly worldwide we are still generations away from seeing a downward turn of the cost and financial problems related to COPD, but this will happen – it is just a case of when rather than if.”

COPD care

COPD is still primarily diagnosed by spirometry – a simple breathing test where people breathe into a tube and it’s measured how efficiently they can breathe air out. The instrument has seen some slight renovations as it has become handheld in the last couple of years and witnessed a drop in price. With a lower cost and a smaller design, the instruments have become fairly automated so it doesn’t take any technical knowledge or training to use.

Russell Bowler is Program Director and Scott Van da Walker is Program Coordinator, of the COPD Program at National Jewish Medical and Research Center. The COPD Program at National Jewish offers comprehensive, individualized care for people with COPD including emphysema and chronic bronchitis.

“Diagnostic criteria for COPD – or the gold standard for diagnosing it in the community is spirometry,” Van da Walker says. “The advances are that these spirometers are now handheld and relatively inexpensive, probably less than a thousand dollars each, so they’re easily accessible to primary care practices to be able to screen for this disease and catch it early before it has a chance to progress.”

Aside from spirometry, there have been some limited advances around diagnostic testing. “Most of the advances have been in imaging, high resolution CAT scans, or learning more about the disease and different forms of the disease,” Bowler says. “The other area would be genetics, a little more in the research arena rather than the clinical arena.”

National Jewish employs a variety of testing modes and instruments in their program. “We do all the modes – high-resolution cat scans, advanced exercise testing, stress testing, advanced lung function studies, genetic testing and so on,” Bowler says. Some of the testing utilized at National Jewish is more elite than others. “There is some testing that we do here that helps us really define the character of somebody’s specific disease such as high resolution CAT scans of the chest and maximal exercise tolerance testing, which is something that’s not readily available outside of the institution,” Van da Walker says. “We do blood studies that look for proteins associated with alpha-1 antitrypsin deficiency that also are not readily available in the community.”

National Jewish is also involved in a number of studies to discover new ways of diagnosis. “From a research standpoint, we have many ongoing studies trying to determine any kind of genetic factors that we can test people to see if they are genetically pre-disposed to develop this lung disease or if there are protein markers we can use to diagnose it even easier or earlier,” Van da Walker says. “That’s not directly related to patient care but that ultimately could lead to much earlier diagnosis.”

In terms of methods of treatment and management of COPD, smoking cessation is still number one. The number two method of treatment for COPD patients is wearing oxygen. “If people require oxygen, wearing oxygen has been demonstrated to prolong life and improve quality of life,” Van da Walker says. “There have also been recent advances in research regarding certain medications such as salmeterol with fluticasone.”

A large study recently completed called TORCH has been the most newsworthy item surrounding COPD. The study indicated that the use of a medicine called Advair may positively impact mortality rates for those suffering from COPD. “We used to think that a medicine under the brand name Advair, which is a combination product with Salmeterol and fluticasone provided quality of life improvements for patients with COPD by making them less out of breath and able to do more things they want to do,” Van da Walker says. “The studies show that there is a possible improvement in overall mortality with the use of this medication so there might be a survival benefit to putting people on these medications earlier than previously.”

“For preserving lung function medium term, combination therapy is certainly the hottest thing right now so doing combination medications such as inhaled corticosteroids and long acting beta agonists,” adds Bowler. “The other hot area is in lung volume reduction, either surgical or bronchoscopic lung volume reduction.”

COPD also promotes management of the disease by simply encouraging people to take better care of themselves; promoting an overall healthy lifestyle, helping people recognize early illness and teaching them how to exercise properly by keeping themselves healthier. “They stay healthier and prolong their life that way,” Van da Walker says.

Recent advances

An estimated 30 - 40 clinical trials related to COPD are underway at National Jewish to explore a variety of new methods of treatment and diagnosis. Studies include examining how giving a low dose of an antibiotic routinely affects complication rates, the effectiveness of inhaled and injectable medications, methods of smoking cessation, new lung volume reduction therapies, and more.

“We’re looking at the use of immune modulators for COPD because COPD is not just a lung disease, it’s a disease of abnormal inflammation. If modifying the immune system can somehow prevent some of the damage that we see in COPD, looking at people that smoke and didn’t smoke with COPD to compare to see if they can identify any factors that contribute to COPD [is going to be helpful],” Van da Walker says.

A couple of recent advances in particular are exciting Bowler and Van da Walker. The news from the TORCH trial regarding the use of salmeterol/fluticasone for a possible potential reduction in mortality has significant implications for the management of the disease. From Bowler’s perspective, studies looking at the genetic basis of those who contract COPD are of great interest. “As an example, in the NY Times there was a big article on the genetics of heart disease and how they discovered a gene associated with heart disease – and the same could be said of COPD,” Bowler says. “There’s some exciting research looking at the genetic basis of why some people smoke and get COPD and why others don’t, and identifying those risk factors.”

Looking to the future

There has been an increased awareness of COPD in the public domain and also in international agencies and governments that the economic and suffering related to COPD is of major significance. Due to increased awareness, it is hoped more resources will be directed to understanding the pathogenesis of COPD and improving the clinical outcome. Asked his prediction for the next 10-20 years regarding COPD, Heffner comments: “We will see new products on the market that may finally control or halt the progression, if not reverse, some of the tissue damage that occurs in COPD and offer opportunities for clinical outcome. Science is going to advance in terms of bringing these new interventions to clinicians, but perhaps more importantly is that we will see worldwide groups such as the American Thoracic Society, the European Respiratory Society (ERS) and the Global Initiative for Chronic Obstructive Lung Disease (GOLD), coming together and coming up with an integrated, co-ordinated effort to disseminate best clinical practices that will penetrate to offices of industrial nations and small clinics and rural parts of the world.”

Heffner: “we are yet to see a downward turn of the epidemic of chronic pulmonary disease in the mortality and morbidity of COPD”

Bowler: “combination therapy is certainly the hottest thing right now”

Van da Walker: “wearing oxygen has been demonstrated to prolong life and improve quality of life”

Dr John Heffner, President of the American Thoracic Society

Russell Bowler, Program Director, COPD Program at National Jewish Medical and Research Center

Scott Van da Walker, Program Coordinator, COPD Program at National Jewish Medical and Research Center