Pulmonary function testing provides the best information to diagnose emphysema.

By Renee DiIulio

dm01.jpg (11069 bytes)The diagnosis of emphysema can be as elusive as the breath its sufferers try to catch. Once a physician suspects chronic obstructive lung disease (COPD), there are just a few tests in the chemistry lab that can assist with differentiating its specific nature and severity. Most of the diagnostic work is handled with pulmonary function testing, and confirmation can be made with computed tomography (CT) scans or surgical examination, a more invasive and risky procedure.

Successful treatment of emphysema is equally elusive. The American Lung Association notes that none of the existing medications for COPD is able to prevent the long-term decline in lung function that is characteristic of this condition; therefore, pharmacotherapy is used solely to treat symptoms. Surgical options, such as lung transplants and lung volume reduction surgery (LVRS), have been found to provide some advantages and are in use more frequently, but the patients who may benefit are restricted.

Laboratory technologists, particularly those who handle pulmonary function testing, are integral to the diagnostic and treatment process. There have not been many advances in their tools, but keen observation can be equally helpful. Denise McElyea, practice manager of the pulmonary lab at University of Texas Medical Branch in Galveston, Tex, notes that a patient’s effort and general background are helpful in interpreting test results.

A Silent Killer
Emphysema does not garner a lot of publicity, but its invisibility does not diminish its effects. The American Association for Respiratory Care (AARC) cites some alarming statistics:

• Worldwide, COPD ranks as the fourth-leading cause of death. The World Health Organization (WHO) estimates COPD is responsible for the death of 2.75 million people each year.

• COPD is also the fourth-leading cause of death in the United States, and is projected to move up to third in 2020.

• In the United States, 16 million adults have been diagnosed, but it is estimated that 30 million Americans actually have COPD.

• Data from the 2000 National Health and Nutrition Examination Survey indicate COPD was responsible for 8 million physician office and hospital outpatient visits, 1.5 million emergency department visits, 726,000 hospitalizations, and 119,000 deaths.

• In 2000, the nation’s annual COPD-related costs were estimated to be approximately $30.4 billion. Health care expenditures accounted for $14.7 billion, and indirect costs, such as decreased income due to loss of work or premature death, were $15.7 billion.1

The American Lung Association notes that emphysema ranks 15th among chronic conditions that contribute to limiting activity. Almost 44% of individuals with emphysema report that their daily activities have been limited by the disease.2

A comprehensive national survey titled Confronting COPD in America found that breathlessness has a strong impact on everyday living, with 28% of respondents experiencing difficulty breathing when sitting or lying still; 32% when talking; 44% when washing or dressing; 46% when doing light housework; and 72% when walking up one flight of stairs. The survey found that 90% of persons diagnosed with COPD had one or more symptoms either every day or most days during their worst 3-month period. Even more worrisome was the finding that a similar percentage (91%) of persons with undiagnosed COPD also reported one or more of these symptoms every day or most days. The researchers determined that 11% of respondents showed symptoms but had not been diagnosed.3

Similar Symptoms
Emphysema is not often suspected immediately because its symptoms mirror those of many other conditions. According to AARC Diagnostic Specialty Section Chair Catherine Foss, RRT, RPFT, these conditions include asthma, congestive heart failure, bronchiectasis, tuberculosis, obliterative bronchiolitis, and diffuse panbronchiolitis.

Most patients present with dyspnea, which is defined as abnormal or uncomfortable breathing in the context of what is normal for a person according to his or her level of fitness and exertional threshold for breathlessness.4 Additional symptoms include cough and limited exercise tolerance.

These symptoms are the result of the destruction of the alveoli, small structures in the lungs where oxygen and carbon dioxide are exchanged, and/or the smallest bronchi, the lung’s breathing tubes. These structures are fragile, and any damage is irreversible. The bronchi can collapse, and the walls of the alveoli may develop small holes causing the lungs to lose their elasticity. Gas exchange slows, stale air becomes trapped, and insufficient oxygen is delivered to the bloodstream.

Emphysema can be further classified into three subtypes based on the affected portion of the acinus, or unit of lung served by the bronchi. Centriacinar emphysema involves the bronchi in the proximal portion of the acinus, is most prominent in the upper lobes, and is closely associated with cigarette smoking. Panacinar emphysema involves all components of the secondary lobe equally and is usually associated with alpha-1-antitrypsin (AAT) deficiency. Distal acinar (paraseptal) emphysema destroys the alveoli, is typically near the pleural surface, and rarely causes significant airway damage.5

It is important to not only diagnose emphysema but to differentiate its type and severity as this may affect treatment options.

Spirometry—Like Gold
Traditionally, COPD has been diagnosed on the basis of patient-reported symptoms. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommends measurement of lung function both to diagnose the disease and to categorize its severity.6 The initiative recommends the use of spirometry, but McElyea notes there is no gold standard. “Every doctor has his own preference,” she says.

The various pulmonary function tests are used to determine the lungs’ characteristics and capabilities. Results are compared to values based on age, weight, height, gender, and race. They look at:

  • Total lung capacity or how much air the lungs can hold.
  • Forced expiratory volume (FVC), defined as how quickly air can be moved in and out.
  • The ability to transfer oxygen from the air into the bloodstream.
  • The ability to remove carbon dioxide.
  • Bronchodilator response.

Though not necessarily the “gold standard” for all, spirometry offers much value. According to Foss, it can be performed in many different settings outside the hospital, such as screening fairs and physicians’ offices, in order to pick up early emphysema and intervene before it becomes advanced.

Spirometers measure the amount of air that can be forced out in one second (FEV1) and the amount of air that can be completely and forcibly exhaled (FVC). The ratio of FEV1/FVC provides an excellent assessment of airway obstruction. Results are typically given in both absolute numbers and as a predicted percentage of normal.7 The GOLD criteria for mild COPD (stage 1) is an FEV1/FVC ratio of less than 70% and FEV1 of greater than or equal to 80% predicted.6

The results, developed using normal values, vary depending on gender, race, age, and height. Though necessary to interpret the results, “normal” values vary for each laboratory, and it is important to assure that the reference formulas used represent the general patient population.7

The test is typically performed three times to ensure reproducibility. It requires that the patient make a maximum effort; and nose clips help to prevent air leaks. McElyea shares that she always notes in the chart when patients have not made their best effort. “You can tell when a patient is not giving it their all, for whatever reasons, and it affects the results of the test,” she says.

Measured before and after a bronchodilator is used, spirometry can help determine the nature of the COPD. If expired volumes and flow rates do not improve after use of a bronchodilator, emphysema is implied though it does not exclude a response to long-term therapy. Generally, an increase of greater than 12% in FEV1 or the FVC is considered significant.8

Spirometry is simple and inexpensive, and it has been suggested that past and current smokers, as well as those exposed to lung hazards in the workplace, undergo regular testing. Some work has been done with office spirometers, which would require less expense and time and would allow easier regular testing.9

Different Tests, Different Concerns
Office spirometry would require confirmation with diagnostic spirometry,9 but similarly, spirometry is typically not the only test performed before a diagnosis of emphysema is reached.

Patients may undergo testing with a peak flow meter, which measures the peak expiratory flow (PEF). The advantages of PEF tests include measurements within a minute (three short blows) using simple, safe, handheld devices that, typically, cost less than $20. On the other hand, disadvantages may outweigh the test’s usefulness in COPD diagnosis: PEF is relatively insensitive to obstructions of the small airways (mild or early obstruction); it is very dependent on patient effort; it has about twice the intersubject and intrasubject variability; and mechanical PEF meters are much less accurate than spirometers.9

A more useful test is pulse oximetry. Using light waves, the test indirectly measures the amount of oxygen in the bloodstream. Though it does not offer as much information as an arterial blood gas (ABG), it can be helpful in providing instant feedback on a patient’s status.10

ABG analyzes directly the amount of oxygen and carbon dioxide in the bloodstream and, therefore, provides excellent information on the acuteness and severity of the condition. Additionally, a pH below 7.3 is a sign of acute respiratory compromise.10

Imaging studies can also provide clues to a patient’s condition. The radiographic features of emphysema include hyperinflation and an arterial deficiency pattern. However, the radiograph is insensitive to the presence of mild emphysema. Evidence shows that high-resolution CT (HRCT) scans are better.5 The finding of abnormally low lung densities on an HRCT lung scan in adult smokers is very highly correlated with the pathologic grading of emphysema and, therefore, may soon be considered a secondary reference for COPD, but high-resolution lung scans are infrequently performed clinically due to their high cost.9

Foss notes that CT scans are playing a larger role in the diagnosis and staging of emphysema than had previously been experienced due to recent advances in technology and capabilities. “High-resolution CT with scoring for asthma severity and 3-D techniques has been used to quantify the degree of emphysema, especially to evaluate for surgery, but not for routine evaluations,” she says.

Gerard J. Criner, MD, professor of medicine with the Pulmonary and Critical Care Medicine Division at Temple University School of Medicine in Philadelphia, and director of the Temple Lung Center at Temple University Hospital, agrees that CT is done more routinely by selected centers when something during therapy is aligned with emphysema. “The evolution in technology has increased our ability to image the lungs and objectify scoring,” he says. Because the speed has increased, he also notes that the exams are better for patients. “Before, patients had to hold their breath for a length of time that was too difficult for them, but now, the scan can be completed in 7 seconds,” he says.

Lab professionals must remain aware of the issue of breathlessness. Whatever tests are run, it’s important to remember that emphysema patients tend to fatigue easily and become very short of breath, according to Foss. “Routine testing takes much longer than hospital administration allows for in the time standards. Lab staff needs to use the time wisely and effectively with this type of patient. The patient may need wheelchair transportation arranged and will need to arrive rested prior to testing; otherwise, the subject may be too tired from walking to the laboratory,” she says.

Inherited or Influenced
Though all of the causes of emphysema are not yet completely understood, the disease is typically related to smoking. Its progression can often be slowed with the cessation of the habit. In some cases, however, emphysema is hereditary and due to a deficiency of the protein alpha-1 antitrypsin (AAT).

The gene for alpha-1 deficiency is recessive, and a patient needs to have inherited it from both parents to suffer from levels of alpha-1 that are deficient. Approximately one in 2,500 people has this inherited deficiency; most of them are of Northern European descent.11

AAT concentration can be determined with a simple blood test. AAT phenotype testing, which may be ordered if concentration is low, looks at the amount and type of AAT produced and compares it to normal patterns. Once an abnormality is determined, DNA testing may be used to establish which Pi gene alleles are present; the test does not check for every variant, just the most common—M, S, and Z, as well as any that may be common in a particular geographical area or family.12 Family members may choose to be tested once the condition is diagnosed to determine their risk, as well as the chances of passing it on to their children.

No Smoking Allowed
ATT patients tend to have emphysema in the lower portions of their lungs, making them poor candidates for lung volume reduction surgery (LVRS), one of the newer surgical treatments for the disease. The procedure reduces the size of the lungs, typically around 20% to 30%, to allow the associated muscles to return to a more normal position, making breathing easier.

A study completed by the National Heart, Lung, and Blood Institute and the Center for Medicare and Medicaid Service found that, on average, patients with severe emphysema who undergo LVRS with medical therapy are more likely to function better after 2 years and do not face increased risk of death compared to those who receive only medical therapy.13 The effects, however, vary widely according to the patient.

The National Emphysema Treatment Trial (NETT) study found that two characteristics helped to determine whether a patient would benefit: the location of the emphysema in the lungs and the patient’s exercise capacity. These characteristics are combined to form four groups of patients:

1) Participants with mostly upper-lobe emphysema and low exercise capacity, who were more likely to live longer and more likely to function better after LVRS than after medical treatment.

2) Participants with mostly upper-lobe emphysema and high exercise capacity, who had no difference in survival; those in the surgical group were more likely to function better than those who received medical treatment without surgery.

3) Participants with mostly non-upper-lobe emphysema and with low exercise capacity, who had similar survival and exercise ability after LVRS as after medical treatment, but had less shortness of breath.

4) Participants with mostly non-upper-lobe emphysema and with high exercise capacity, who had poorer survival after LVRS than after medical treatment.13

As a result of the findings, Medicare reassessed its coverage for the surgery and now provides reimbursement. Criner, an investigator in the trial, notes that, as usual, most other insurers followed its lead. The surgery is limited, however, not only to those who are most likely to benefit but also to those who have quit smoking. Criner says that older but consistent data show that if a patient had surgery but continued to smoke, the benefits lasted only a year and a half rather than 5 years or more. “There is no point in undergoing the risks of surgery for such a low benefit,” he adds.

Tests for cotinine, a by-product of nicotine found in the bloodstream of smokers, can determine whether a patient has quit smoking or not. The cessation of smoking is the single most important change an emphysema patient can make, unless the condition is related to AAT deficiency. However, success at quitting smoking can be as elusive as all other issues related to emphysema.

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13. National Emphysema Treatment Trial (NETT): Evaluation of lung volume reduction surgery for emphysema. Department of Health and Human Services; National Institutes of Health; National Heart, Lung, and Blood Institute. Available at: http://www.nhlbi.nih.gov/health/prof/lung/nett/lvrsweb.htm#lvrs. Accessed August 24, 2004.