MONTREAL--Regular use of low-dose inhaled corticosteroids decreases the risk of death from asthma, a new study suggests.[1] The findings also indicate that irregular use or discontinuation of inhaled corticosteroids may be harmful.

While inhaled corticosteroids are considered effective treatments for asthma, studies of their ability to prevent death from the disease had been inconclusive. However, previous investigations did not take into account regularity of use, Samy Suissa, PhD, a Professor of Epidemiology at McGill University in Montreal, explained in a recent interview with PULMONARY REVIEWS.

To determine whether and to what extent the use of inhaled corticosteroids prevents asthma deaths, Dr. Suissa and colleagues analyzed information on 30,569 asthma patients (age 5 to 44 years) who were members of a health insurance plan based in Saskatchewan, Canada. All patients had received at least three prescriptions for an antiasthma medication in any one-year period between September 1975 and December 1991. The patients were followed until age 55 years, death, end of insurance coverage, or December 31, 1997.

A total of 77 people died from asthma during follow-up. Eleven of these subjects were excluded from the analysis because they died at a time when the health plan did not collect data on medication usage.

The remaining 66 subjects were compared with 2,681 control subjects who were matched for duration of follow-up until time of death in the case subjects (index date), date of enrollment into the health plan (± 3 months), and severity of asthma.

DECREASED RISK OF DEATH

Regular use of inhaled corticosteroids--such as one canister every couple of months--was associated with a decreased risk of death from asthma (Figure 1). In contrast, sporadic use appeared to increase the risk.

The researchers calculated that the rate of death from asthma declined 21% with every additional canister of inhaled corticosteroids used during the year before the index date (ie, time of death in the case subjects). A 54% reduction was established for every additional canister used during the six months before the index date. In addition, the rate of asthma deaths among patients who used more than six canisters per year was 50% lower than it was among patients who did not use inhaled corticosteroids.

"The benefits occur at doses of corticosteroids that are lower than those associated with adverse ocular effects in adults and with decreased growth in children," the researchers emphasized. In fact, almost all of the patients who used inhaled corticosteroids were prescribed low-dose beclomethasone (ie, 50 µg of drug delivered per puff).

REGULAR USE IS ESSENTIAL

Patients who stopped taking inhaled corticosteroids within three months before the index date were significantly more likely to die than were those who continued to use the drugs (adjusted rate ratio, 4.6). Patients who discontinued corticosteroids more than three months before the index date also had an increased risk of death, but the differences did not reach significance.

"The patients were started on these drugs because they needed them. The fact that they stopped taking the drugs shows that clearly, they didn't allow sufficient time for the steroids to take their effect. The untreated disease itself likely caused the increases in asthma deaths," Dr. Suissa told PULMONARY REVIEWS. "Essentially, when you start taking these medications you are being protected and reduce your risk of death. But if you stop taking them, the risk goes right back up."

The excess risk of death associated with discontinuation of therapy is not linked to adrenal insufficiency--a potential complication of abrupt cessation of oral corticosteroids--because the doses of inhaled corticosteroids used by most of the subjects were too low to cause this effect, the researcher added.

STUDY IMPLICATIONS

Dr. Suissa believes that these findings "will give physicians an impetus not to fear inhaled corticosteroids and to recommend them strongly to patients." Furthermore, said Dr. Suissa, "I think the stronger message will be to the patients who have not been using these drugs appropriately. The information from our study should reinforce to patients the notion that, even though they will not feel an instant relief from inhaled corticosteroids, these drugs will save their lives and make their asthma better. They have to understand that regularity of use is crucial."

--Kristin Della Volpe

Reference
1. Suissa S, Ernst P, Benayoun S, et al. Low-dose inhaled corticosteroids and the prevention of death from asthma. N Engl J Med. 2000;343:332-336.

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