Course

Chapter 1: Definition

Key Points:

·        COPD is a disease state characterized by airflow limitation that is not fully reversible. The airflow limitation is usually both progressive and associated with an abnormal inflammatory response of the lungs to noxious particles or gases.

·        The four-stage classification of COPD severity used throughout this report provides an educational tool and a general indication of the approach to management. This conceptual framework also emphasizes that COPD is usually progressive if exposure to the noxious agent is continued.

·        The characteristic symptoms of COPD are cough, sputum production, and dyspnea upon exertion.

·        Chronic cough and sputum production often precede the development of airflow limitation by many years and these symptoms identify individuals at risk of developing COPD.

·        The focus of this Workshop Report is primarily on COPD caused by inhaled particles and gases, the most common of which worldwide is tobacco smoke.

·        COPD can coexist with asthma, the other major chronic obstructive airway disease characterized by an underlying airway inflammation. However, the inflammation characteristic of COPD is distinct from that of asthma.

·        Pulmonary tuberculosis may affect lung function and symptomatology and, in areas where tuberculosis is prevalent, can lead to confusion in the diagnosis of COPD.

Definition

For years, clinicians, physiologists, pathologists, and epidemiologists have struggled with the definitions of disorders associated with chronic airflow limitation, including chronic bronchitis, emphysema, chronic obstructive pulmonary disease (COPD), and asthma. The definitions of these terms variably emphasize structure and function and are often based on whether the term is used for clinical or research purposes. For example, epidemiologists have created terminology and criteria, based on functional status, that can be monitored in population-based studies or studies of physicians’ diagnoses^1,2.

Based on current knowledge, a working definition of COPD is: a disease state characterized by airflow limitation that is not fully reversible. The airflow limitation is usually both progressive and associated with an abnormal inflammatory response of the lungs to noxious particles or gases. Symptoms, functional abnormalities, and complications of COPD can all be explained on the basis on this underlying inflammation and the resulting pathology.

The chronic airflow limitation characteristic of COPD is caused by a mixture of small airway disease (obstructive bronchiolitis) and parenchymal destruction (emphysema), the relative contributions of which vary from person to person. Chronic inflammation causes remodeling and narrowing of the small airways. Destruction of the lung parenchyma, also by inflammatory processes, leads to the loss of alveolar attachments to the small airways and decreases lung elastic recoil; in turn, these changes diminish the ability of the airways to remain open during expiration. Airflow limitation is measured by spirometry, as this is the most widely available, reproducible test of lung function.

Many previous definitions of COPD have emphasized the terms "emphysema" and "chronic bronchitis," which are no longer included in the definition of COPD used in this report. Emphysema, or destruction of the gas-exchanging surfaces of the lung (alveoli), is a pathological term that is often (but incorrectly) used clinically and describes only one of several structural abnormalities present in patients with COPD. Chronic bronchitis, or the presence of cough and sputum production for at least 3 months in each of two consecutive years, remains a clinically and epidemiologically useful term. However, it does not reflect the major impact of airflow limitation on morbidity and mortality in COPD patients. It is also important to recognize that cough and sputum production may precede the development of airflow limitation; conversely, some patients develop significant airflow limitation without chronic cough and sputum production.

Natural History

COPD has a variable natural history and not all individuals follow the same course. However, COPD is generally a progressive disease, especially if a patient’s exposure to noxious agents continues. If exposure is stopped, the disease may still progress due to the decline in lung function that normally occurs with aging. Nevertheless, stopping exposure to noxious agents, even after significant airflow limitation is present, can result in some improvement in function and will certainly slow or even halt the progression of the disease.

Classification of Severity: Stages of COPD

For educational reasons, a simple classification of disease severity into four stages is recommended (Figure 1-2). The staging is based on airflow limitation as measured by spirometry, which is essential for diagnosis and provides a useful description of the severity of pathological changes in COPD. Specific FEV₁ cut-points (e.g.,< 80% predicted) are used for purposes of simplicity: these cut-points have not been clinically validated.

The impact of COPD on an individual patient depends not just on the degree of airflow limitation, but also on the severity of symptoms (especially breathlessness and decreased exercise capacity) and complications of the disease. A wide range of FEV₁ values are included in Stage II: Moderate COPD, reflecting the major contribution of these additional factors to the disability caused by COPD. For the purposes of management, this category is subdivided into two segments (IIA and IIB), as discussed in Chapter 5.3, Manage Stable COPD, and Figure 5-3-8. The management of COPD is largely symptom driven, and there is only an imperfect relationship between the degree of airflow limitation and the presence of symptoms. The staging, therefore, is a pragmatic approach aimed at practical implementation and should only be regarded as an educational tool, and a very general indication of the approach to management. “All FEV₁ values refer to post-bronchodilator FEV₁.”

Although COPD is defined on the basis of airflow limitation, in practice the decision to seek medical help (and so permit the diagnosis to be made) is normally determined by the impact of a particular symptom on a patient’s lifestyle. Thus, COPD may be diagnosed at any stage of the illness.

The characteristic symptoms of COPD are cough, sputum production, and dyspnea upon exertion. Chronic cough and sputum production often precede the development of airflow limitation by many years, although not all individuals with cough and sputum production go on to develop COPD. This pattern offers a unique opportunity to identify those at risk for COPD and intervene when the disease is not yet a health problem. A major objective of GOLD is to increase awareness among healthcare providers and the general public of the significance of these symptoms.

·        Stage 0: At Risk— Characterized by chronic cough and sputum production. Lung function, as measured by spirometry, is still normal.

·        Stage I: Mild COPD—Characterized by mild airflow limitation (FEV₁/FVC < 70% but FEV₁ > 80% predicted) and usually, but not always, by chronic cough and sputum production. At this stage, the individual may not even be aware that his or her lung function is abnormal. This underscores the importance of healthcare providers doing spirometry in all smokers so that their lung function can be observed and recorded over time.

·        Stage II—Moderate COPD: Characterized by worsening airflow limitation (30% < FEV₁ < 80% predicted), and usually the progression of symptoms with shortness of breath typically developing on exertion. This is the stage at which patients typically seek medical attention because of dyspnea or an exacerbation of their disease. The division into stages IIA and IIB is based on the fact that exacerbations are especially seen in patients with an FEV₁ below 50% predicted. The presence of repeated exacerbations has an impact on patients’ quality of life and requires appropriate management.

·        Stage III—Severe COPD: Characterized by severe airflow limitation (FEV₁ < 30% predicted) or the presence of respiratory failure or clinical signs of right heart failure. Respiratory failure is defined as an arterial partial pressure of oxygen (PaO₂) less than 8.0 kPa (60 mm Hg) with or without arterial partial pressure of CO₂ (PaCO₂) greater than 6.7 kPa (50 mm Hg) while breathing air at sea level. Respiratory failure may also lead to effects on the heart such as cor pulmonale (right heart failure). Clinical signs of cor pulmonale include elevation of the jugular venous pressure and pitting ankle edema. “Patients may have severe (Stage III) COPD even if the FEV₁ is > 30% predicted, whenever these complications are present.” At this stage, quality of life is very appreciably impaired and exacerbations may be life threatening.

Variable Course of COPD

The common statement that only 15-20% of smokers develop clinically significant COPD is misleading. A much higher proportion develops abnormal lung function at some point if they continue to smoke. Not all individuals with COPD follow the classical linear course as outlined in the Fletcher and Peto diagram, which is actually the mean of many individual courses^3.

Figure 1-3 shows four examples of the various courses that individual COPD patients may follow. Panel A illustrates an individual who has cough and sputum production, but never develops abnormal lung function (as defined in his Report). Panel B illustrates an individual who develops abnormal lung function but who may never come to diagnosis. Panel C illustrates a person who develops abnormal lung function around age 50, then progressively deteriorates over about 15 years and dies of respiratory failure at age 65. Panel D illustrates an individual who develops abnormal lung function in mid-adult life and continues to deteriorate gradually but never develops respiratory failure and does not die as a result of COPD.

Scope of the Report

The focus of this Report is primarily on COPD caused by inhaled particles and gases, the most common of which worldwide is tobacco smoke. Poorly reversible airflow limitation associated with bronchiectasis, cystic fibrosis, tuberculosis, or asthma is not included except insofar as these conditions overlap with COPD.

Asthma and COPD

COPD can coexist with asthma, the other major chronic obstructive airway disease characterized by an underlying airway inflammation. Asthma and COPD have their major symptoms in common, but these are generally more variable in asthma than in COPD. The underlying chronic airway inflammation is also very different (Figure 1-4): that in asthma is mainly eosinophilic and driven by CD4+ T lymphocytes, while that in COPD is neutrophilic and characterized by the presence of increased numbers of macrophages and CD8+ T lymphocytes. In addition, airflow limitation in asthma is often completely reversible, either spontaneously or with treatment, while in COPD it is never fully reversible and is usually progressive if exposure to noxious agents continues. Finally, the responses to treatment of asthma and COPD are dramatically different, in terms of both the overall magnitude of the achievable response and the qualitative effects of specific treatments such as anticholinergics and glucocorticosteroids. However, there is undoubtedly an overlap between asthma and COPD. Individuals with asthma who are exposed to noxious agents that cause COPD may develop a mixture of “asthma-like” inflammation and “COPD-like” inflammation. There is also evidence that longstanding asthma on its own can lead to airway remodeling and partly irreversible airflow limitation. Asthma can usually be distinguished from COPD, but until the causal mechanisms and pathognomonic markers of these diseases are better understood it will remain difficult to differentiate the two diseases in some individual patients. Given the current state of medical and scientific knowledge, an attempt to determine an absolutely rigid definition of COPD or asthma is bound to end up in semantics.

Pulmonary Tuberculosis and COPD

In many developing countries both pulmonary tuberculosis and COPD are common. In countries where tuberculosis is very common, respiratory abnormalities may be too readily attributed to this disease. Conversely, where the rate of tuberculosis is greatly diminished, the possible diagnosis of this disease is sometimes overlooked.

Chronic bronchitis/bronchiolitis and emphysema often occur as complications of pulmonary tuberculosis and are important contributors to the mixed lung function changes characteristic of tuberculosis⁴. The degree of obstructive airway changes⁵ in treated patients with pulmonary tuberculosis increases with age, the amount of cigarettes smoked, and the extent of the initial tuberculous disease⁶. In patients with both diseases, COPD adds to the disability of pulmonary tuberculosis, and vice versa.

Therefore, in all subjects with symptoms of COPD, a possible diagnosis of tuberculosis should be considered, especially in areas where this disease is known to be prevalent. Investigations to exclude tuberculosis should be a routine part of COPD diagnosis, the intensity of the diagnostic procedures depending on the degree of suspicion. Chest radiograph and sputum culture are helpful in making the differential diagnosis.

References

1.        Samet JM. Definitions and methodology in COPD research. In: Hensley M, Saunders N, eds. Clinical epidemiology of chronic obstructive pulmonary disease. New York: Marcel Dekker; 1989. p. 1-22.

2.        Vermeire PA, Pride NB. A “splitting” look at chronic non-specific lung disease (CNSLD): common features but diverse pathogenesis. Eur Respir J 1991; 4:490-6.

3.        Fletcher C, Peto R. The natural history of chronic airflow obstruction. BMJ 1977; 1:1645-8.

4.        Leitch AG. Pulmonary tuberculosis: clinical features. In: Crofton J, Douglas A, eds. Respiratory diseases. Oxford: Blackwell Science; 2000. p. 507-27.

5.        Birath G, Caro J, Malmberg R, Simonsson BG. Airway obstruction in pulmonary tuberculosis. Scand J Resp Dis 1966; 47:27-36.

6.        Snider GL, Doctor L, Demas TA, Shaw AR. Obstructive airway disease in patients with treated pulmonary tuberculosis. Am Rev Respir Dis 1971; 103:625-40.

Course