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Can Early Treatment of COPD Slow Its Progression?
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Key Point |
Controversy surrounds the issue of whether early recognition and treatment of COPD makes a difference in its progression. |
CHICAGO—At a Clinical Controversy session during the American College of Chest Physicians’ 2007 Annual International Scientific Assembly, Sandra G. Adams, MD, of the University of Texas Health Sciences Center and Paul Enright, MD, of the University of Arizona presented opposing views as to whether early treatment of COPD can slow disease progression.
PRO: PATIENTS ARE IDENTIFIED TOO LATE
Dr. Adams presented a case for early identification and treatment. She described a prospective study of 153 consecutive hospitalized patients, 95% of whom were admitted for nonrespiratory complaints and 9% who had a COPD diagnosis on admission. Bedside spirometry performed during the study revealed COPD in 26% of patients.
Spirometry results were provided to the treating physicians only by request: Ultimately, 70% of patients were never diagnosed with obstructive lung disease by hospital discharge, including 11% of patients who had very severe COPD (ie, FEV1 < 30% predicted).
“Depending on the population you look at, between 10% and 60% of newly diagnosed COPD patients have an FEV1 of less than 50% predicted,” Dr. Adams lamented. “We’re diagnosing them much too late.”
Dr. Adams cited the case of a 49-year-old smoker who denied shortness of breath and cough. The patient attributed her “tiredness” and reduced activity to aging, and divulged her “smoker’s cough” only upon further questioning. Regularly seen by her primary care physician for hypertension, the patient’s COPD went undetected until she was hospitalized. It was only then that her FEV1 was revealed to be 28% predicted.
However, not only patients with severe disease display symptoms: Those with moderate COPD often are symptomatic, too, Dr. Adams pointed out. She described the case of a 62-year-old former smoker with FEV1 of 63% predicted prebronchodilator who uses a golf cart because he is no longer able to walk the course with his friends.
Overdiagnosis is less important to Dr. Adams than full evaluation of patients. She pointed out that some experts believe that COPD should be defined by an FEV1/FVC below the lower limit of normal, rather than a fixed FEV1/FVC of less than 70%. Citing studies by Mannino et al, Dr. Adams said that the risk of respiratory-related hospitalization is significantly increased in older patients, whether a ratio below the lower limit of normal or a fixed ratio of less than 70% is used. She urged careful history taking to reveal symptoms and improve early diagnosis, and she advised maintenance pharmacotherapy to raise FEV1, reduce exacerbations, and improve dyspnea, endurance, and quality of life.
CAN MEDICATION CHANGE THE COURSE OF DISEASE?
Dr. Adams described a study in which patients with a mean FEV1 of 73% experienced significant increases in lung function with tiotropium. She also cited research to show that long-acting formoterol improves breathlessness, chest tightness, cough, and sleep, that tiotropium increases exercise endurance, and that adding long-acting bronchodilators to albuterol prescribed as needed is beneficial to symptomatic patients with FEV1 of less than 80%.
Her own tiotropium data in maintenance therapy–naïve patients showed improvement in dyspnea, St. George’s Respiratory Questionnaire scores, and trough FEV1, over one year, while the placebo group showed poorer outcomes. In a “compelling” post hoc analysis of this data, tiotropium patients had a 12.4-mL/year decrease in trough FEV1 versus a 58.0-mL/year decrease among patients in the placebo group. For further evidence, Dr. Adams advised the audience to “stay tuned” for the results of the 6,000-patient, $100 million UPLIFT (Understanding Potential Long-term Impacts on Function with Tiotropium) trial due next year.
Dr. Adams also argued for reducing exacerbation risk through use of long-acting b-agonists (LABAs) and long-acting anticholinergics, inhaled corticosteroids (ICS), and LABA/ICS combinations. In closing, she asked, “If it were you with an FEV1 of 70% predicted and you had had an exacerbation, would you want to stay on albuterol alone?”
CON: THE BEST COPD DRUG ADDRESSES SMOKING CESSATION
Dr. Enright began by saying he is evaluating quality of spirometry in a varenicline study, referring to it as “the best COPD drug that there is.” He endorsed smoking cessation at any stage as the one intervention proved to affect loss of lung function and all-cause mortality—whether or not smokers have COPD—with bupropion and varenicline, the only medications to change rate of decline. Using them doubles or quadruples cessation rates, said Dr. Enright.
He noted that smokers comprise 50% of inhaler trial participants, with little help to quit provided. He wondered why large, multimillion-dollar studies are conducted to evaluate effects of tiotropium on FEV1 decline, when the Lung Health Study showed anticholinergics have no such effect—with active drugs’ mortality rates double that of placebo. He presented data to show that there is no difference in loss of FEV1 between smokers with FEV1 of 90% and 75% predicted over five years.
EARLY COPD DETECTION IS A MISUSE OF EFFORTS
Dr. Enright said that false-positive rates with spirometry are high, especially those based on Global Initiative for Chronic Obstructive Lung Disease (GOLD) guideline criteria in patients older than 60. He warned of adverse consequences: increased costs due to follow-up testing and inappropriate prescription of medications, adverse effects of such medications, labeling of patients as “sick,” and loss of confidence in allopathic medicine.
Research shows that spirometry does not motivate smokers to quit, Dr. Enright contended. Furthermore, while primary care physicians initially are excited to use spirometers in their practices, only 20% continue over time despite low costs and good reimbursement, he noted. This decline in use has been attributed to lack of time.
GOLD STAGE 1 IS NOT A DISEASE STATE
Lung Health Study data show that smokers in GOLD stage 1 do not rapidly lose FEV1 and that those with mildly low lung function with some obstruction do not necessarily develop COPD, Dr. Enright said, adding that mild COPD is not a disease and does not increase risk of respiratory morbidity or death. He stressed that inhalers are not indicated for and should not even be considered in smokers until their FEV1 falls below 50% predicted and they have dyspnea.
Contrary to Dr. Adams’ claim that smokers with early COPD have increased mortality, Dr. Enright contended that only patients in stages 2, 3, and 4 have significantly increased mortality rates, due primarily to cardiovascular mortality. Dr. Enright said early-stage symptoms are respiratory in origin. He attributed dyspnea and shortness of breath to cardiovascular disease, obesity, metabolic syndrome, or poor cardiovascular conditioning.
Dr. Enright contrasted the cost of spirometry at $25 per person with $150-per-month inhalers for the 25% of patients with “COPD” who had normal results. He expressed concern that expensive medications are unnecessarily prescribed in early stages to try to reduce a few exacerbations.
“In the Canadian COPD guidelines, tiotropium is indicated in mild disease. There just isn’t the evidence. Stay tuned, but don’t hold your breath for the UPLIFT trial,” he warned.
Quoting Barnes and Stockley, Dr. Enright said, “No currently available treatments reduce the progression of COPD or suppress the inflammation in small airways and lung parenchyma.” He added that pipeline drugs will not reduce the decline. He challenged the strength of Dr. Adams’ tiotropium study of “mild” disease, stressing that it was a post hoc analysis of a small subgroup of patients who had FEV1 levels that increased into the normal range.
Dr. Enright claimed that one-third of pre-bronchodilator obstruction is not COPD, but may indicate asthma. Often, he says, time does not permit postbronchodilator spirometry, and many who do receive postbronchodilator testing do not have COPD. He wondered whether the pharmaceutical industry influences clinical practice guidelines that recommend tiotropium for mild COPD.
REBUTTALS
Dr. Adams agreed that smoking cessation slows disease progression and that mild COPD should not be treated with maintenance inhalers. However, she pointed out that data from the Lung Health Study showed that the mortality risk among participants with mild disease was similar to those with more severe disease. She agreed that much of this mortality could be attributed to cardiovascular events, but much was related to respiratory factors. In addition, she countered that as many as 20% to 30% of hospitalizations for acute exacerbations of COPD may be for patients with moderate—as opposed to severe—disease. Medications to treat COPD, particularly bronchodilators, can significantly decrease the need for costly hospitalizations, she added. Dr. Enright suggested that a smoker with inflammation and normal FEV1 has chronic bronchitis, not COPD, and that generic antibiotics are best to treat that. He reiterated the importance of helping patients to stop smoking, instead of prescribing inhaled corticosteroids and bronchodilators.
—Beth Tansey Peller, RN
Suggested Reading
Adams SG, Anzueto A, Briggs DD Jr, et al. Tiotropium in COPD patients not previously receiving maintenance respiratory medications. Respir Med. 2006;100(9):1495-1503.
Anzueto A, Tashkin D, Menjoge S, Kesten S. One-year analysis of longitudinal changes in spirometry in patients with COPD receiving tiotropium. Pulm Pharmacol Ther. 2005;18(2):75-81.
Barnes PJ, Stockley RA. COPD: current therapeutic interventions and future approaches. Eur Respir J. 2005;25(6):1084-1106.
Buffels J, Degryse J, Decramer M, Heyrman J. Spirometry and smoking cessation advice in general practice: a randomised clinical trial. Respir Med. 2006;100(11):2012-2017.
Halpern MT, Stanford RH, Borker R. The burden of COPD in the U.S.A.: results from the Confronting COPD survey. Respir Med. 2003;97 Suppl C:S81-S89.
Lusuardi M, De Benedetto F, Paggiaro P, et al. A randomized controlled trial on office spirometry in asthma and COPD in standard general practice: data from spirometry in Asthma and COPD: a comparative evaluation Italian study. Chest. 2006;129(4):844-852.
Mannino DM, Homa DM, Akinbami LJ, et al. Chronic obstructive pulmonary disease surveillance—United States, 1971-2000. MMWR Surveill Summ. 2002;51(6):1-16.
Mannino DM, Sonia Buist A, Vollmer WM. Chronic obstructive pulmonary disease in the older adult: what defines abnormal lung function? Thorax. 2007;62(3):237-241.
Scanlon PD, Connett JE, Waller LA, et al. Smoking cessation and lung function in mild-to-moderate chronic obstructive pulmonary disease: the Lung Health Study. Am J Respir Crit Care Med. 2000;161(2 Pt 1):381-390.
Zaas D, Wise R, Wiener C; Longcope Spirometry Investigation Team. Airway obstruction is common but unsuspected in patients admitted to a general medicine service. Chest. 2004;125(1):106-111.
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