The GOLD Standard for Chronic Obstructive Pulmonary Disease

Nicholas J. Gross

Stritch-Loyola School of Medicine and Hines VA Hospital, Hines, Illinois

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Few would doubt that chronic obstructive pulmonary disease (COPD) is as great a challenge for physicians today as it ever was. We know the facts all too wellit is the fourth leading cause of death in the United States and many other Western countries, and a major cause of morbidity with a huge impact on quality of life. Its cost is enormous and will increase over the foreseeable future. These and other statistics are a constant reminder that we, that is, society in general and the medical profession in particular, are not doing very well with COPD, as is pointed out in the preface of the important article by Pauwels and coworkers in this issue of the Journal (1). The fact that much greater strides have been made in most of the other major chronic diseases in recent decadesdiabetes, coronary heart disease, hypertension, and peptic ulcer disease come most readily to mind  is not just embarrassing but is evidence that we have not done nearly enough to uncover the science behind COPD that is needed to devise new and more effective ways to address this disease.

At the risk of belaboring the point, in the last decade for example, for each of the other major diseases I mentioned, at least one and, in some cases, several entirely new classes of drugs and new devices or interventions have been approved, as well as new ways of using preexisting drugs. Outcomes for these diseases have generally improved (2). By contrast, not a single entirely new class of drugs, device, or procedure has been approved for COPD in the last decade. True, there are some potential new agents in development (3). True, one long-acting -agonist and one combination of existing bronchodilators have been approved, and one pre-existing drug has been approved for smoking cessation. These have had an impact on therapy. Gains have also been made in pulmonary rehabilitation, sleep-disordered breathing, and mechanical ventilation, and lung volume reduction surgery has become widely practiced although perhaps not fully accepted yet. Against these gains, some of our former mainstays have lost ground. Methylxanthines have been demoted to third-line drugs in stable COPD (4) and inhaled corticosteroid maintenance therapy, widely employed but never approved for this use in the United States, has been shown by four large, impeccably conducted studies to have quite limited benefit (e.g., Reference 5). Score these as negatives, and our therapeutic options have not increased. Moreover, the outcome statistics for COPD remain essentially unchanged (2). If our treatment of COPD today is any better than it was a decade ago, and I think it probably is, this is mainly because it is more refined, not because we have any radically new or better treatments.

Instead, we pulmonologists have had to work "smarter" with what we have, striving to ensure that accepted wisdom is more widely disseminated, better understood, and more consistently applied. To this end, guidelines and standards for COPD management began to appear in many countries in the middle 1990s. The Global Initiative for Chronic Obstructive Lung Disease (GOLD), the executive summary of which is published in this issue (1), is the latest and most detailed of these. It is a document that will be the standard reference for many years. More than this, it is a challenge with an international voice " to increase awareness. . . improve prevention and management of COPD through a concerted worldwide effort. . . and to encourage. . . renewed research." One hopes it achieves all these goals, particularly the last.

Why has progress in COPD been relatively so slow? The GOLD initiative points to a number of reasons. COPD differs from most other major diseases in that irreversible damage is inexorably accumulating for many decades before the disease presents clinically. We have little to offer during this long preclinical phase other than smoking cessation. This advice is regretfully widely ignored, probably because smokers are aware of the wide differences in susceptibility to the effects of smoking and each probably hopes that he (or she, as is increasingly the case) will yet escape the disease. But one group of smokers that heeds the antismoking message is the group that learns they have ₁-antitrypsin deficiency. For them, it's not a case of if they will develop a crippling disease, but when. Perhaps this is the key to early interventionto identify susceptibility factors. Given this wide variation in susceptibility to smoking- related COPD, there must be a number of susceptibility traits like ₁-antitrypsin deficiency and these traits are probably discoverable by molecular techniques. We need to know what these are so that we can routinely screen smokers at a preclinical stage and target our antismoking message to the most susceptible subjects in a "not-if-but-when" manner. Is it fantasy to imagine that we will one day send a blood sample to the laboratory for a "COPD susceptibility profile," much as we now send for a lipid profile to detect and prevent arterial disease?

We also need to know a great deal more about the molecular and cellular biology of established COPD so that we can arrest the ongoing airway damage. Its mechanisms are quite different from those in asthma and refractory to the anti-inflammatory modalities that work in asthma (6).

Perhaps most ambitious, we need ways to reverse established COPD and promote restructuring and regrowth of alveoli in the adult lung. Ridiculous? Impossible? Maybe not (7, 8). If it can be done in animals, why not in humans?

If there is a single message that the GOLD initiative conveys, it is that we could do better if we knew more about the basic science of COPD. Research, as always, is the key to better management. We need to set the bar higher and be much more ambitious in our research goals if we are to make significant progress toward conquering this major disease in subsequent decades.

	References

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1. Pauwels RA, Buist AS, Calverley PMA, Jenkins CR, Hurd SS. on behalf of the GOLD Scientific Committee. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: NHLBI Global Initiative for Chronic Obstructive Lung Disease (GOLD) Workshop Summary. Am J Respir Crit Care Med. 2001; 163: 1256-1276 [Free Full Text].

2. National Heart, Lung, and Blood Institute. Morbidity and mortality: chartbook on cardiovascular, lung, and blood diseases. Bethesda, MD: U.S. Department of Health and Human Services, Public Health Service, National Institutes of Health; 1998.

3. Barnes PJ. Novel approaches and targets for the treatment of chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1999; 160: 72S-79S .

4. American Thoracic Society. Standards for the diagnosis and care of patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1995;152:S77-S120.

5. Lung Health Study Research Group. Effect of inhaled triamcinolone on the decline in pulmonary function in chronic obstructive pulmonary disease. N Engl J Med 2000;343:1902-1909.

6. Barnes PJ. Inhaled corticosteroids are not beneficial in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2000; 161: 342-344 [Free Full Text].

7. Massaro G, Massaro D. Retinoic acid treatment abrogates elastase-induced pulmonary emphysema in rats. Nat Med 1997; 3: 675-677 [Medline].

8. Belloni PA, Garvin L, Mao C-P, Bailey-Healy I, Leaffer D. Effects of all-trans-retinoic acid in promoting alveolar repair. Chest 2000;117 (Suppl 1):235S-241S.