Gold globe

In 2006, the US National Heart, Lung, and Blood Institute and the World Health Organization published a revised guideline, the Global Initiative for Chronic Obstructive Lung Disease,1 to update the original version published in 2001. This guideline, known as the GOLD report, is valuable to those caring for patients with chronic obstructive pulmonary disease (COPD). The guideline was updated by international experts from the fields of pulmonary medicine, allergy, immunology, and asthma who evaluated the best evidence related to COPD diagnosis, management, and prevention. The GOLD report Web site1 makes available the full report and other resources, including an executive summary, a pocket guide for health care professionals, and a patient guide.

Definition Changes

COPD is a growing problem worldwide. It is ranked as the fourth leading cause of chronic morbidity and mortality in the United States and is expected to rank fifth in the overall burden of diseases in the world.1 The GOLD report names the major cause of COPD as tobacco smoking, but acknowledges that this is not the only cause of COPD and notes that, in some parts of the world, it is not the major cause. Moreover, the fact that not all smokers will develop COPD opens the door to research into molecular and cellular mechanisms and immunology as they relate to lung disease. The 2006 GOLD report provides a revised working definition of COPD and now recognizes it as a preventable and treatable disease. This more positive definition should encourage more research on the prevention of COPD and more work on creating an effective program for managing the disease (making it treatable). Although COPD is not curable, when exposure to noxious agents (such as cigarette smoke) stops, the disease may slow, or even stop, its progression. Still, once the disease is present, it will need to be treated on an ongoing basis.

The 2006 definition points to the pulmonary component of COPD as chronic airflow limitation that is not fully reversible, thus distinguishing COPD from asthma, which is described as “airflow obstruction within the lung that is often reversible either spontaneously or with treatment”2 in the recent revision of the Global Initiative for Asthma report. The new definition of COPD also mentions extrapulmonary effects that may contribute to COPD’s severity; these include cachexia, skeletal-muscle wasting, increased cardiovascular disease, anemia, osteoporosis, and depression. The working definition of COPD ends with the statement, “the airflow limitation is usually progressive and associated with an abnormal inflammatory response of the lung to noxious particles or gases.”1 This wording is also in the 2001 GOLD report, but the 2006 guidelines go further in addressing the inflammation related to COPD.

Classification Changes

The 2001 GOLD report classified COPD into four levels, defined using spirometry, with particular emphasis on forced expiratory volume in 1 second (FEV1) divided by forced vital capacity (FVC) and on the percentage of the predicted value represented by the FEV1 result. The 2006 report has four divisions, but has changed the characteristics of the stages and has dropped the first level (Table 1). The 2006 report continues to use the same fixed ratio of 0.7 for FEV1/FVC (measured after bronchodilator use) to define obstruction. The report mentions that this is a recognized problem, since the ratio decreases as a normal function of aging; using a fixed ratio may lead to overdiagnosis of COPD in the older, healthy population. The report adds that “postbronchodilator reference values in this population are urgently needed to avoid potential overdiagnosis.”1

Table 1: Comparison of the 2001 and 2006 classifications of severity
2001 Stages 2001 Criteria 2006 Stages 2006 Criteria
Stage 0: At Risk Normal spirometry results
Chronic symptoms
(cough, sputum production)
Stage I: Mild FEV1/FVC<0.7
FEV1 ≥80% predicted
With or without chronic symptoms
(cough, sputum production)
Stage I: Mild FEV1/FVC<0.7
FEV1 ≥80% predicted
Stage IIA: Moderate FEV1/FVC<0.7
50% ≤FEV1 <80% predicted
With or without chronic symptoms
(cough, sputum production)
Stage II: Moderate FEV1/FBC<0.7
50% ≤FEV1 <80% predicted
Stage IIB: Moderate FEV1/FVC<0.7
30% ≤FEV1 <50% predicted
With or without chronic symptoms
(cough, sputum production)
Stage III: Severe FEV1/FVC<0.7
FEV1 <30% predicted or <50% predicted plus respiratory failure or clinical signs of right heart failure
Stage III: Severe FEV1/FVC<0.7
30% ≤FEV1 <50% predicted
Stage IV: Very Severe FEV1/FVC<0.7
*FEV1 <30% predicted or <50% predicted plus chronis respiratory failure

Postbronchodilator values are used. FEV1 = forced expiratory volume in 1 second and FVC = forced vital capacity. Both 2001 and 2006 classifications define respiratory failure as Pao2 of less than 60 mm Hg, with or without a Paco2 of more than 50 mm Hg, while breathing room air at sea level.

The Burden of COPD

The 2006 GOLD report ties the prevalence of COPD to tobacco smoking, but adds that air pollution has taken over the role of primary risk factor in many parts of the world. Based on standardized methods of examining the prevalence of COPD (and including spirometry in the evaluation), it is now estimated that up to 25% of all adults over 40 years old may be classified as having COPD at stage I (mild) or higher. This is a striking number, particularly since less than 6% of the population have been told that they have COPD. Review and meta-analysis of data gathered in 28 countries between 1990 and 2004 (plus an additional study from Japan) have shown that COPD’s prevalence is much higher in smokers and former smokers than in nonsmokers. Those over 40 years old have a much higher incidence of COPD, and COPD rates for men are appreciably higher than rates for women. In 2000 in the United States, however, women had a higher death rate than men from COPD; for Canada, the same situation is predicted.1

The worldwide burden of COPD is expected to increase due to continued exposure to risk factors and the changing age demographic. The Baby Boom population is now moving into the over-60 age range; beginning at this age, COPD starts to show a clinically significant impact on health. In addition, life expectancy worldwide is increasing, so more people will reach the age at which COPD develops. The GOLD report explores the financial burden of COPD, citing a 1987 report that the per-capita cost of hospitalization for patients with COPD in the United States was 2.7 times that of patients without the disease. Another study of Medicare patients over 65, published in 1998, reported that per-capita expenditures for people with COPD ($8,482) were 2.5 times those of people without COPD ($3,511).1

Risk Factors

Cigarette smoking is the number one risk factor worldwide for COPD (Table 2). The GOLD report includes a discussion of the interaction between genetic makeup and the environment to explain why two people with the same smoking history will have different COPD outcomes. The person who is more genetically susceptible to the damaging effects of cigarette smoke will probably develop COPD, while another may not. The report also discusses the possible impact of gender on smoking and on occupational/environmental exposures to particles that can lead to the development of COPD. In particular, the report discusses the impact of burning wood and other biomass fuels (such as animal dung, crop residue, and coal) in open fires or stoves in poorly ventilated dwellings. Indoor air pollution carries a higher COPD risk for women and children in developing countries due to their increased exposure, compared with that of men.1

Both the 2001 and 2006 reports discuss the genetic risk factor of a1 antitrypsin deficiency, as well as the potential for any factor that negatively affects the lungs during the growth and maturing process, to increase the risk for COPD. The 2006 report has a discussion of oxidative stress and a section on nutrition that were not in the 2001 report. When the balance between oxidants and antioxidants is disrupted (increasing oxidant levels and/or reducing antioxidant levels), there appears to be an increase in the risk of COPD. The discussion on the impact of nutrition ties malnutrition, weight loss, starvation, anabolic/catabolic states, and anorexia nervosa to emphysema and emphysematous changes.

For the 2006 report, more emphasis is given to the role of inflammation in COPD. A chart lists the differences among COPD, asthma, and severe asthma in

  • the activation of particular cells (for example, neutrophils, macrophages, and T cells);
  • which key mediators are released (such as interleukin 8 or interleukin 5 versus nitric oxide);
  • the role of oxidative stress;
  • the different sites of disease (airway, parenchyma, or blood vessel); and
  • the response to therapy (small versus large responses to bronchodilators, for example, and good versus poor responses to steroids).

The 2006 report also discusses the tie between COPD and systemic changes in the body, such as cachexia, osteoporosis, depression, and anemia.

Table 2: Risk factors for chronic obstructive pulmonary disease.1
Genetic Disposition Susceptibility to damage from exposure to particles α1 antitrypsin deficiency
Exposure to Particles Tobacco smoke
Occupational dusts (organic and inorganic)
Indoor air pollution from heating/cooking with biomass fuels in poorly ventilated dwellings
Outdoor air pollution
Other Risk Factors Lung growth and development
Oxidative stress
Gender
Age
Respiratory infections
Socioeconomic status
Nutrition
Comorbidities

Management of COPD

Both the 2001 and the 2006 GOLD reports break management down into four steps: assess and monitor disease, reduce risk factors, manage stable COPD, and manage exacerbations. These components have been brought up to date, based on the latest published research, and the new categories (stages I through IV) are linked to the various management strategies (Table 3). The 2006 report has also added several drugs that were not covered in the 2001 report. They include such combination medications as albuterol/iprotropium and salmeterol/fluticasone, a relatively new bronchodilator (tiotropium), four commonly used inhaled glucocorticosteroids, and two commonly used systemic glucocorticosteroids, among others. The addition of the six steroids provides a much stronger link to the working definition of COPD that describes the disease as airflow limitation that is usually progressive and associated with an abnormal inflammatory response. This shows that the management of COPD is being altered to address inflammation as having a larger role. In the management strategy, the addition of inhaled steroids occurs at stages III and IV if the patient has a history of repeated exacerbations (at least three exacerbations in the past 3 years). An exacerbation is defined as “an event in the natural course of the disease characterized by a change in the patient’s baseline dyspnea, cough, and/or sputum that is beyond normal day-to-day variations, is acute in onset, and may warrant a change in regular medication in a patient with underlying COPD.”1

The final chapter of the 2001 report discussed future research; this topic is addressed throughout the 2006 report and was not given its own chapter. Instead, the last chapter in the 2006 report discusses the problems associated with getting the recommendations adopted into primary care. High-quality spirometry is encouraged for COPD diagnosis, but the report acknowledges that this may be impossible in many areas of the world. Testing using a peak-flow meter may be considered, but has a low specificity for COPD because many other diseases (or poor performance) can cause low peak-flow results.1

The 2006 report discusses the increased likelihood of comorbidities in older patients. These include ischemic heart disease, lung cancer, pulmonary hypertension, and heart failure in the cardiopulmonary system, as well as prostate cancer, depression, diabetes mellitus, Parkinson disease, dementia, and arthritis in other areas. These comorbid conditions can increase the negative impact of COPD and can add complications to managing COPD. This chapter recognizes the role of the primary care practitioner in promoting the reduction of risk factors and mentions that many are participating in public-health campaigns to reduce indoor and outdoor pollution, control exposure to occupational dusts, and promote smoking cessation.

Table 3: Therapy for each stage of chronic obstructive pulmonary disease
Stage I: Mild Stage II: Moderate Stage III: Severe Stage IV: Very Severe
FEV1/FVC<0.7 FEV1/FVC<0.7 FEV1/FVC<0.7 FEV1/FVC<0.7
FEV1≥80% predicted 50%≤FEV1<80% predicted 30%≤FEV1<50% predicted FEV1<30% predicted or FEV1<50% predicted plus chronic respiratory failure
 –––––––––––– Active reduction of risk factors; influenza vaccination. –––––––––––––––>
 ––––––––––––––– Add short-acting bronchodilator when needed. –––––––––––––––––>
Add regular treatment with one or more long-acting bronchodilators (when needed); add rehabilitation.
ADd inhaled glucocorticoids if the patient is having repeated exacerbations.
Add long-term oxygen therapy if chronic respiratory failure is present. Consider surgical treatments.

FEV1 = forced expiratory volume in 1 second and FVC = forced vital capacity. FEV1 is assessed using postbronchodilator values. From the Global Initiative for Chronic Obstructive Lung Disease.1 Adapted by teh author.

Conclusion

The GOLD 2006 report is a valuable tool that should be studied by those working with COPD patients. Implementing its guidelines can help standardize practice based on best evidence and help clinicians give effective, high-quality education to the COPD patient and family. The report is thorough, concise, and accurate, with a full bibliography to support its evidence-based recommendations. COPD is moving into prominence worldwide, but new developments in drug treatment and increased use of pulmonary rehabilitation can improve patients’ lives, reduce symptoms, affect exacerbations, and reduce hospitalizations. Smoking cessation is an important goal for slowing and stopping the progression of the disease (and can help reduce the exposure of others to secondhand smoke). Given the high number of adult patients with COPD, and the amount of help that they need from RTs, it makes sense for RTs to take time to read the 2006 GOLD report and its recommendations in their work. The benefits are many, for both the patient and the RT.

Bill Pruitt, RRT, AE-C, CPFT, is senior instructor, Department of Cardioresiratory Sciences, University of South Alabama, Mobile; PRN respiratory therapist, Springhill Medical Center and Mobile Infirmary Medical Center, Mobile; and a delegate in the American Association for Respiratory Care House of Delegates. For further information, contact [email protected]

References

  1. GOLD, the Global Initiative for Chronic Obstructive Lung Disease. Available at: www.goldcopd.com. Accessed July 6, 2007.
  2. Welcome to GINA, the Global Initiative for Asthma. Available at: www.ginasthma.org. Accessed July 6, 2007.

STRAIGHT TALK

John Power, MBA

RT had the opportunity to discuss the latest market trends in aerosol delivery with John Power, MBA, I. Eng MIED (Member of the Institute of Engineering Designers [UK]), and managing director of Aerogen Ireland Ltd, Galway, Ireland. Aerogen is a specialty medical device company that develops and manufactures a broad range of nebulizers and other aerosol drug delivery devices. Power holds qualifications in computer, mechanical, and production engineering, as well as an MBA from Oxford Brookes University, Oxford, England.

RT: Please tell us about the latest technology trends that Aerogen is seeing in the aerosol delivery market today.

Power: There are three common types of aerosol generators for inhaled drug delivery: nebulizers, metered-dose inhalers, and dry powder inhalers. In today’s aerosol-delivery market, a lot of [pressure] is placed on the developers and manufacturers to deliver medication in a timely manner and to improve the ease-of-use profile of such devices. The latest trends include device refinement to improve aerosol delivery of existing therapies and, thereby, improve patient compliance. The result of this is the evolution of more sophisticated, yet easy-to-use delivery modalities, which in turn is helping to drive research into pulmonary delivery of traditionally nonpulmonary-targeted drugs; for example, hormones, pain management therapy, aerosol gene therapy, etc.

RT: How have Aerogen’s products incorporated these trends?

Power: Aerogen has led the way in the field of high-technology nebulization with the advent of our micropump-based nebulizers in 2002. We have incorporated micropump technology, often referred to as vibrating mesh technology, into our range of nebulizers (Aeroneb® Professional, Aeroneb Solo, Aeroneb Go) through the use of our patented OnQ™ aerosol generator. Our nebulizers do not require additional airflow to generate an aerosol. They effectively nebulize a broad spectrum of medications ranging from aqueous drugs to suspensions. They do not generate heat and, therefore, do not degrade biologically based compounds. All of these characteristics increase the ease-of-use profile of our devices and make them attractive to patients, to caregivers, and indeed to many biotechnology and drug companies, which are investigating their use as part of a drug/device indication.

RT: Aerogen recently introduced its Aeroneb Solo single-patient-use nebulizer. What features will future generations of disposables have that will make disposable nebulizers even more effective and efficient than they already are?

Power: Future trends for disposable nebulizers should lead to device development based on clinical requirements that results in easy-to-use efficient nebulizers. For example, a general-purpose nebulizer for use with neonate patients needs to be small, lightweight, and quiet if it’s to be tolerated within the close environment of a ventilated infant. Disposable nebulizers will need to have broad-spectrum utility with the ability to efficiently nebulize a wide range of drug formulations. They cannot hinder the RT, and therefore must be easy to set up and operate. Difficult assembly and triggering of unnecessary alarms waste the RT’s time and do not enhance patient care. Multifunctionality, such as the ability to deliver both continuous and intermittent therapy, will result in increased convenience for the RT. As such, future disposable nebulizers need to fully complement the overall objectives of in-line nebulization; that is, to get to the patient better, faster, and with the minimum intervention from an RT.