Hot Topics in Respiratory Medicine - Editor-in-chief: Marc Miravitlles

Summary

• COPD GUIDELINES
• COPD DEFINITION OVER TIME
• AIRFLOW LIMITATION
• Airflow limitation reversibility
• Classification of severity
• REFERENCES

Full text

Chronic obstructive pulmonary disease (COPD) is a common chronic disorder and a major worldwide health problem, which is predicted to become the third leading cause of death in the world by 2020. The past decade has witnessed an increasing interest in COPD, and this disease is currently the focus of intense research because the prevalence and mortality rates are still rising. Although COPD is not a new disease, over the years its name, definition, and diagnostic criteria have evolved. Fortunately, major expert panels and international societies of respiratory diseases have agreed on a common definition and developed guidelines for COPD diagnosis, staging, and management [1-4]. The present review focuses on the COPD definition, diagnostic criteria, and staging system.

COPD GUIDELINES

The first intent to standardize concepts, definitions, and diagnostic criteria for COPD took place in Great Britain in the late 1950s [5] and thereafter in the United States [6]. However, the first clinical practice guidelines for the assessment and management of patients with COPD were published 30 years ago [7,8]. These and subsequent clinical guidelines were mainly consensus recommendations based on expert opinion and available studies, and they have been criticized for being inconsistent and not explicitly evidence-based. Probably the earliest consensus that received widespread dissemination was the one published by Hodgkin and coworkers in 1975 [8]. This consensus report reflected the state of the art of its time, both in the scientific understanding of COPD and in the clinical approach to patient care. Most of the therapeutic interventions have changed over the years, and a few of the included topics are no longer considered relevant, but nearly all of the concepts and modalities discussed in that publication remain in the current guidelines. It stressed the primary role of spirometry in confirming the presence of airflow obstruction in order to confirm the diagnosis of COPD. Spirometry is currently a diagnostic prerequisite for the diagnosis of COPD in the new generation of guidelines. Although an increasing number of research articles on COPD and its management appeared over the subsequent years, very few new guidelines were published until the 1990s.
In 1995, the American Thoracic Society (ATS) published a position paper entitled, " Standards for the Diagnosis and Care of Patients with Chronic Obstructive Pulmonary Disease (COPD)" [9]. This ATS statement was widely accepted and disseminated; it provided an effective road map for the detection, staging, and management of COPD and offered guidance for the care of patients with COPD under special circumstances (surgery, sleep disorders, air travel, and end-of-life decisions). During the same year, the European Respiratory Society (ERS) published its views on the assessment and management of patients with COPD [10] and in 1997 the British Thoracic Society (BTS) published its own guidelines [11].
In 2001, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) published its guidelines [2]. This was a collaborative effort, between the National Heart, Lung, and Blood Institute (NHLBI) and the World Health Organization (WHO), aimed at increasing awareness of COPD around the globe. This evidence-based report was offered as a guideline for the detection and management of COPD and is the first of a new generation of rigorous, evidence-based COPD documents. Revisions were made in 2003 and 2005 [3-4].
In 2004, ATS and the ERS revised their guidelines recognizing the importance of the recommendations from GOLD guidelines; however, ATS/ERS enhanced their own guidelines to specifically address oxygen therapy, pulmonary rehabilitation, noninvasive ventilation, surgery in and for COPD, sleep, air travel, and end of life [1]. The new guidelines also placed special emphasis on smoking-related issues because smoking represents the single most important preventable cause of COPD in the developed world. Although the ATS/ERS recommendations are similar to the guidelines developed by GOLD, they provide considerably more clinical detail. In addition, the new recommendations emphasize the systemic features of COPD above and beyond its pulmonary consequences. The ATS/ERS document places greater emphasis on the prevention and treatment of COPD, and they contain much more information for COPD patients than do the GOLD guidelines.

COPD DEFINITION OVER TIME

Over the years several different definitions have been offered for COPD. It name was proposed by two American doctors, MH Williams and NS Seriff [12], to describe a disease entity combining chronic bronchitis and pulmonary emphysema, manifested in patients by progressive airflow obstruction with breathing-related symptoms such as chronic cough, exertional dyspnea, expectoration, and wheeze.
Chronic bronchitis has been defined in clinical terms as "productive cough that is present for a period of 3 months in each of 2 consecutive years in the absence of another identifiable cause of excessive sputum production" [9].
Emphysema, in contrast, has been defined by its pathological description as "an abnormal enlargement of the air spaces distal to the terminal bronchioles accompanied by destruction of their walls and without obvious fibrosis" [9].
The 1995 ATS statement defined COPD as "a disease state characterized by chronic airflow limitation due to chronic bronchitis and emphysema; the airflow obstruction is generally progressive, may be accompanied by airway hyperreactivity, and may be partially reversible" [9].
From the same year, the ERS defined COPD as

... a disorder characterized by reduced maximum expiratory flow and slow forced emptying of the lungs, features which do not change markedly over several months. Most of the airflow limitation is slowly progressive and irreversible. The airflow limitation is due to varying combinations of airway disease and emphysema; the relative contribution of the two processes is difficult to define in vivo [10].

While the ATS and ERS definitions of COPD emphasize chronic bronchitis and emphysema, GOLD in 2001 proposed a definition of COPD that focused on the physiology (progressive nature of airflow limitation), the pathology (airway inflammation), and etiology (noxious particles or gases) [2]. The GOLD guidelines indicated that COPD should not refer to a disease combining chronic bronchitis and pulmonary emphysema, but rather to "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." Two important points are worth noting. First, inflammation is the driving mechanism behind the abnormalities in the airways of patients with COPD. Second, from a review of data from all over the world, it is clear that tobacco is not the only cause of COPD, and one can regard COPD as an overall abnormal reaction to many different particles. In some areas of the world where biomass fuel is used as a source of energy primarily for cooking, persons exposed to the particles can develop airflow obstruction that is indistinguishable from that characteristic of COPD [13-15]. This definition, which depends on physiologic changes rather than on a clinical diagnosis, makes it much easier to classify never-smokers as having COPD.
The initial GOLD definition, as well as those published by ATS and ERS, focuses exclusively on the lung abnormalities [2,9,10]. This situation has changed since several studies have provided evidence that COPD is often associated with significant extrapulmonary manifestations, the so-called systemic effects of COPD.
The new ATS/ERS guidelines, like the GOLD guidelines, have redefined COPD as "a preventable and treatable 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, primarily caused by cigarette smoking." Although COPD affects the lungs, it also produces significant systemic consequences [1,4].
It is now clear that apart from the deleterious effects on the lungs, the disease is associated with several systemic manifestations, which are clinically relevant [16-23]. Systemic manifestations of COPD are now recognized as an important feature of the disease and contribute significantly to decreased exercise capacity, decreased health status, and increased mortality of COPD patients [20,24-28]. It is now recognized that 20 to 50% of patients with COPD (depending on the severity of the disease) manifest systemic involvement, such as peripheral muscle dysfunction, low body mass index, and muscle depletion as characterized by low fat-free mass index and poor functional capacity.
The other important aspect of the new COPD definition is the change in the connotation with negative characteristics that have led to a dangerous nihilistic attitude toward the disease. COPD is defined spirometrically as airflow limitation that is not fully reversible. This limitation is documented with the use of the forced expiratory volume in 1 s (FEV₁), which fails to improve with a bronchodilator. In a paradoxical way, there have been many studies designed to reverse what we have defined as being not fully reversible. It is no surprise that the lack of substantial change in FEV₁ to many different therapeutic agents has resulted in a nihilism that is not deserved [2,9,10,29-32]. The measurement of outcomes different from the FEV₁ is important because it changes the way in which the course of the disease can be defined. Based on this concept, several medical therapies that failed to show changes in FEV₁ have demonstrated improvement in other outcomes, such as rate of exacerbation, dyspnea, and health status, all of which are of extreme importance to patients suffering from COPD. These contradictory findings can be reconciled by acknowledging that COPD is not just a pulmonary disease and is therefore incompletely described by the FEV₁. Currently, there are important specific therapeutic interventions for COPD with documented benefits in outcomes different to the FEV₁ (dyspnea, exercise capacity, health-related quality of life, exacerbation, or mortality) that make COPD not only a preventable but also a treatable disease.

AIRFLOW LIMITATION

Airflow limitation is the slowing of expiratory airflow as measured by spirometry, with a persistently low FEV₁ and FEV₁/forced vital capacity (FVC) ratio despite treatment. The 1995 ATS COPD definition did not specify a value of FEV₁/FVC ratio as airflow limitation [9]. However a previous ATS document specified that a FEV₁/FVC ratio lower than the fifth percentile of the normal population indicates the presence of airflow limitation [33]. The ERS (1995) defined airflow limitation as a FEV₁/FVC ratio of 88% predicted for men and 89% for women [10]. The GOLD and the ATS/ERS definition indicate that COPD diagnosis is confirmed by spirometry. The presence of a postbronchodilator FEV₁/FVC ≤0.7 confirms the presence of airflow limitation that is not fully reversible [1,2].

Airflow limitation reversibility

As mentioned earlier, COPD is currently defined by the presence of airflow limitation that shows little or no improvement after inhaled bronchodilator drugs. Several criteria have been proposed to define a significant bronchodilator response. The 1995 ATS definition of COPD does not specifically define reversibility [9], although a previous ATS statement classified reversibility as an FEV₁ increase of 200 mL and 12% above baseline FEV₁ after inhaled bronchodilators [33]. The ERS definition of COPD classified reversibility as a 10% improvement in percent of predicted FEV₁ after a bronchodilator [10]. The GOLD criteria, like that of the ATS, use a change of >12% and 200 mL above baseline FEV₁ after inhaled bronchodilators or inhaled corticosteroids [2].
The term partial reversibility is frequently mentioned but not fully defined in the GOLD and ATS/ERS documents as well. In the context of the definitions, partial reversibility probably defines patients who have reversibility in response to either corticosteroids or bronchodilators (as defined earlier), but their best FEV₁ and FEV₁/FVC classify them as having airflow limitation.

Classification of severity

Because the degree of FEV₁ reduction has prognostic implications and correlates with mortality and morbidity, a staging system based on the degree of airflow obstruction has been proposed by the different international guidelines for COPD classification. As reviewed in Table 1, ATS/ERS and GOLD have developed staging systems for COPD based on the value of FEV₁ % predicted [1,2].

TABLE 1. Staging systems of the American Thoracic Society/European Respiratory Society and Global Initiative for Chronic Obstructive Lung Disease for chronic obstructive pulmonary disease

Both systems propose 5 stages for COPD classification, from mild (stage I) to very severe (stage IV) and introduce a stage 0 (chronic cough and phlegm without airflow obstruction) that includes subjects "at risk" of developing the disease.
A population-based study of COPD in Latin America, called the PLATINO study (Proyecto Latinoamericano de Investigación en Obstrucción Pulmonar), showed the prevalence of COPD staging according to the GOLD definition [34]. The prevalence of all the stages showed a substantial variation across the countries: stage 0 ranged from 20% in Montevideo to 33% in Santiago, stage I from 5.2% in Mexico City to 12.5% in Montevideo, stage II from 1.9% in Mexico City to 6.4% in Montevideo, stage III from 0.5% in Mexico City to 0.9% in Sao Paulo, and stage IV from 0.1% in Caracas and Montevideo to 0.3% in Santiago. Similar distribution has also been reported in high-income countries. Figure 1 shows the prevalence of COPD according to GOLD severity strata by countries reported in the PLATINO study.

Figure 1. Prevalence of chronic obstructive pulmonary disease according to the Global Initiative for Chronic Obstructive Lung Disease severity strata in the PLATINO study.

Although the severity of COPD is currently assessed using a single physiological measurement-the FEV₁-it is well known that COPD is associated with a range of other local and systemic clinical manifestations such as dyspnea, exercise limitation [35], pulmonary hypertension [36], peripheral muscle weakness [37], and malnutrition [20]. Furthermore, FEV₁ is not the only predictor of mortality in COPD. Several studies have identified other risk factors such as hypoxemia or hypercapnia [38,39], exercise capacity [40,41], degree of functional breath-lessness [42], peripheral muscle abnormalities [28], and a low body mass index [20]. Therefore, grading COPD solely on FEV1 limits our capacity to fully express the degree of severity and does not reflect the clinical manifestations of the disease and its ultimate prognosis. Indeed, the ATS/ERS statement on COPD expressed the need for a multicomponent staging system that in addition to the degree of impairment incorporates the perceptive and the systemic consequences of COPD. It was felt that such a grading system could help categorize and grade the heterogeneous manifestations of patients with this common disorder.
Using the FEV₁, the disease has been classified arbitrarily in five stages (see Table 1). This classification has proven useful in epidemiological and large group and drug studies, but the simple grading by spirometry fails to fully represent the different dimensions that are affected by the disease. COPD could be represented as a pulmonary disease that affects several domains: the respiratory, perceptive, and systemic domain as summarized in Figure 2.

Figure 2. Chronic obstructive pulmonary disease (COPD) domains.

All of these domains can be evaluated with relatively simple instruments that have been validated over time and provide important independent prognostic information [20,40-42]. The multidimensional index BODE-body mass index (B), percentage of predicted FEV₁ (O), dyspnea (D), and 6-min walk distance (E)-is a tool that has proven to be a better predictor of all cause (cardiovascular, respiratory, cancer, and others) and disease-specific mortality than is FEV₁ [43]. Table 2 shows the variables point values used to calculate the BODE Index. Further studies have shown that the variables contributing to the index are amenable to change by interventions and thus make the BODE a potential tool to use in the evaluation of disease-modifying interventions [44-46]. Ong and coworkers [44] reported that the BODE scoring system was a better predictor of hospitalization for COPD than were the GOLD staging criteria based largely on FEV₁. In another study, Imfeld and coworkers [45] investigated whether the BODE index was able to predict survival in patients undergoing lung volume reduction surgery (LVRS). Their results indicate that the postoperative BODE index was a better predictor of survival than was FEV₁, dyspnea score, or 6-min walk distance. These results are consistent with those reported by Cote and Celli [46], who found that the BODE index improves after pulmonary rehabilitation and that the magnitude of the change was predictive of survival. These findings argue that COPD is not just a pulmonary disease and is therefore incompletely described by the FEV₁. In addition, the findings support the use of a multicomponent staging system for outcomes assessment and predicting survival in COPD. More importantly, the evidence accumulated suggests that an optimistic attitude is justified and that there is hope for patients who suffer from this prevalent disease.

TABLE 2. Variables and point values used in the BODE index

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