DETROIT--Daily doses of inhaled corticosteroids do not appear to slow the decline in lung function associated with chronic obstructive pulmonary disease (COPD).

Such anti-inflammatory therapy, however, does reduce the respiratory symptoms, airway reactivity, and rates of unscheduled physician visits and hospitalization experienced by patients with COPD.

Those are the implications of a recent clinical trial of inhaled triamcinolone for the treatment of COPD.[1] "We wanted to see if inhaled anti-inflammatories impact the course of this disease in the same way they are thought to impact the course of asthma," said Michael S. Eichenhorn, MD, one of the principal investigators of the study, in an interview with PULMONARY REVIEWS. "Many COPD patients are given anti-inflammatories, yet nobody has really ascertained the effect of these medications on COPD."

The trial included 1,116 COPD patients, ages 40 to 69 years, who had previously participated in or been screened for the Lung Health Study, a multicenter investigation of the effect of smoking cessation and inhaled bronchodilator use on lung function decline in smokers with airflow obstruction.[2] Participants in the triamcinolone study had a forced expiratory volume in one second (FEV1) of 30% to 90% of the predicted value and an FEV1 to forced vital capacity (FVC) ratio below 0.70. All were smokers or had quit smoking only within the past two years.

Patients were excluded from the trial if they had neuropsychiatric disorders or serious medical conditions other than COPD, such as cancer, recent myocardial infarction, or insulin-dependent diabetes mellitus, or if they had used oral or inhaled corticosteroids or inhaled bronchodilators in the past year. "Thus, we effectively excluded people with symptomatic asthma," the investigators noted in their study.

The patients were randomly assigned to receive triamcinolone or placebo via metered-dose inhaler. Each group was instructed to take six inhalations twice a day (resulting in a total daily dose of 1,200 µg triamcinolone in the treatment group [100 µg per inhalation]).

The investigators assessed compliance every three months through patient interviews and by weighing used inhaler canisters. At the same time, the patients were asked about respiratory symptoms and side effects and given new inhalers.

Every six months, the patients underwent spirometry and were questioned about medical care that they had received since the last follow-up. Records of any hospitalizations, emergency department visits, and nonroutine physician visits were obtained by the investigators.

The patients also were instructed on improving inhaler technique and warned about poor pulmonary function caused by smoking. Patients who wished to quit were referred to smoking-cessation programs and given transdermal nicotine patches if they had a prescription from their physicians.

All patients completed questionnaires about respiratory symptoms at the first six-month follow-up visit and then annually. They underwent methacholine challenge at the nine- and 33-month visits and filled out a 36-item general health survey once a year.

The rate of FEV1 decline was the primary outcome measure. Secondary outcomes included respiratory symptoms, cause-specific morbidity and mortality, airway reactivity to methacholine, and quality of life as it relates to general health. In a substudy of 412 patients, the investigators measured bone density in the lumbar spine and femoral neck at baseline and at one and three years after the start of treatment or placebo.

The two groups were well matched in baseline characteristics, with both exhibiting mild-to-moderate pulmonary function abnormalities, similar rates of respiratory symptoms, and similar degrees of airway reactivity to methacholine. The mean pretreatment FEV1 was only slightly better in the triamcinolone group (2.16 L, 64.9% predicted) than in the placebo group (2.10 L, 63.4% predicted).

During follow-up, which averaged 40 months, treatment compliance rates for the triamcinolone and placebo groups were each about 69% according to patient report, but only 54% and 59%, respectively, according to canister weight.

At the end of the study, most of the outcome measures were similar in the two groups; both overall mortality and quality of life scores were comparable. The two groups also had similar declines in lung function: the mean decreases in FEV1 and FVC were 44.2 and 50.6 mL/y, respectively, for triamcinolone users and 47.0 and 42.3 mL/y, respectively, for placebo recipients.

However, the triamcinolone group had fewer new or worsening respiratory symptoms (21.1 per 100 person-years vs 28.2 in the placebo group) and markedly less airway reactivity to methacholine during the study. In addition, the treatment group had lower rates of unscheduled physician visits for respiratory symptoms (1.2 per 100 person-years vs 2.1 in the placebo group) and fewer hospitalizations for respiratory symptoms (0.99 per 100 person-years vs 2.1 in the placebo group).

Reports of easy bruising tended to be more common among triamcinolone users, although the difference was nonsignificant. Also, the bone density substudy linked triamcinolone with increased bone demineralization of the lumbar spine and femoral neck after three years.

It is unclear if the study findings apply to other dosages of triamcinolone or to other inhaled corticosteroids, such as budesonide or fluticasone, said Dr. Eichenhorn, Head of the Divisions of Pulmonary and Critical Care Medicine, Allergy, and Immunology at Henry Ford Hospital, in Detroit. "Clearly, though, inhaled triamcinolone has no routine role in COPD treatment," he said.

--Timothy Begany

References
1. The 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.

2. Anthonisen NR, Connett JE, Kiley JP, et al. Effects of smoking intervention and the use of an inhaled anticholinergic bronchodilator on the rate of decline of FEV1: the Lung Health Study. JAMA. 1994;272:1497-1505.

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