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Abstract & Commentary
Synopsis: This study of 1116 patients with mild-to-moderate COPD found inhaled triamcinolone did not slow the rate of decline in FEV1, nor did it have any effect on overall mortality. However, inhaled triamcinolone decreased airway reactivity, the symptom of dyspnea, and decreased physician visits and hospitalizations for respiratory complaints.
Source: The Lung Health Study Research Group. N Engl J Med. 2000;343:1902-1909.
Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality in the United States and is characterized by a progressive decline in pulmonary function. Cessation of smoking has been found to slow down the rate of decline, but less than half of patients succeed in quitting. Airway inflammation is felt to be a contributing factor in the pathophysiology of COPD; however, unlike asthma, the data on the use of inhaled steroids has been inconsistent. The authors in this study hypothesized inhaled steroids would decrease the rate of decline of pulmonary function in patients with COPD.
These are the results of the Lung Health Study Research Group. They conducted a multicenter, randomized, placebo-controlled trial using inhaled triamcinolone. The patients had an FEV1/FVC ratio of less than 0.70 and an FEV1 30-90% of predicted. All were current smokers or quit no more than 2 years prior. Exclusion criteria included use of bronchodilators or oral or inhaled steroids within the previous year. The patients received either placebo or inhaled triamcinolone dosed at 6 inhalations twice daily for a total daily dose of 1200 mg/d. Spirometry was performed before and after 2 doses of isoproterenol. In addition, the subjects underwent methacholine bronchial provocation.
A total of 1116 patients were enrolled (559 treatment, 557 placebo) whose average age was 56 years old. The average FEV1 prior to bronchodilator administration was 64.1% of predicted, and the mean duration of follow-up was 40 months. There was no significant difference in the decline of FEV1 between the treatment group and placebo group either before bronchodilator use (decline of 48.6 mL/y for treatment and 49.9 mL/y for placebo) or after bronchodilator use (decline of 44.2 mL/y for treatment and 47 mL/y for placebo). However, the triamcinolone group had less reactivity to methacholine at 9 and 33 months (P = .02). Using the American Thoracic Society—Division of Lung Disease questionnaire, the authors found the only significant improvement in the treatment group was dyspnea (P = .02). Complaints of cough, phlegm production, and wheezing did not significantly improve in the treatment group. Overall, mortality did not improve in the treatment group (15/559 vs 19/557 for the placebo group; P = .49), nor was there an improvement in the quality-of-life score for the treatment group.
The frequency of visits to the emergency room was no different between the two groups for either respiratory or nonrespiratory conditions (P = .36 for respiratory conditions; P = .17 for nonrespiratory). However, there were less unscheduled physician visits and hospitalizations for respiratory conditions in the treatment group (outpatient visits per 100 person-year: 1.2 for treatment group, 2.1 for placebo; P = .03). In terms of side effects, the triamcinolone group had a significantly higher percentage decrease in bone mineral density at the lumbar spine and femoral neck when compared to placebo.
Comment by David Ost, MD & Charles Scott Hall, MD
The use of inhaled corticosteroids in COPD remains questionable despite their widespread use for this condition.1 A recent study from Denmark concluded there was no clinical benefit from inhaled budesonide in terms of either FEV1 or symptoms.2 A larger European study (the ISOLDE trial) found, although there was no effect on the rate of decline of FEV1, inhaled steroids produced a small increase in FEV1 after bronchodilators, less exacerbations, and slower decline in health status.3 There is also evidence that inhaled steroids produce short-term improvements in FEV1, but these effects are not sustained beyond 9 months.4 The Lung Health Study Research Group found that triamcinolone did not affect the rate of decline of FEV1 when compared to placebo; however, airway reactivity, dyspnea, and health care use did improve. The authors felt that although they did not exclude asthma, by excluding patients who regularly use bronchodilators or corticosteroids, they disqualified patients with clinically significant asthma. The use of triamcinolone in this study was also associated with a significant decrease in bone mineral density from baseline. This emphasizes that clinicians must weigh the risks and benefits of using inhaled steroids in their COPD population. In patients with refractory COPD who require frequent urgent visits, a trial of inhaled corticosteroids may be warranted. For those with more stable disease, fewer urgent visits, and higher risk of osteoporosis, inhaled corticosteroids may not be of benefit. (Dr. Hall is a Fellow in Pulmonary and Critical Care Medicine, North Shore University Hospital-NYU School of Medicine, Manhasset, NY.)
1. Jackevicius CA, Chapman KR. Ann Pharmacother. 1997;31:160-164.
2. Vestbo J, et al. Lancet. 1999;353:1819-1823.
3. Burge PS, et al. BMJ. 2000;320:1297-1303.
4. Pauwels RA, et al. N Engl J Med. 1999;340:1948-1953.