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Dying to catch your breath?

MagazineApril 2009 (Vol. 20 Issue 1)Dying to catch your breath?

For years, the drug companies have steadfastly assured patients with asthma that long-term corticosteroids are safe as long as you don't take them by mouth: when inhaled, they don't have the same effects as their oral cousins

For years, the drug companies have steadfastly assured patients with asthma that long-term corticosteroids are safe as long as you don't take them by mouth: when inhaled, they don't have the same effects as their oral cousins.

Yet, over the years, the evidence has revealed that inhaled steroids come with a coterie of adverse effects that are every bit as serious as those of oral steroids. And now there's evidence that they may even prove fatal.

The latest study, by epidemiologists from McGill University in Montreal, Canada, analyzed the hospitalization and prescription records of 175,906 Canadian patients with COPD. They found that 23,942 had been hospital-ized for pneumonia (Am J Resp Crit Care Med, 2007; 176: 162-6). On studying the prescribing history of these patients and comparing them with more than 95,000 control patients, they began to discern a pattern.

Admission rates for pneumonia increased sharply when patients were given steroids; indeed, the higher the dose, the more likely the patient was to develop pneumonia that required a hospital stay. The high-dose patients were taking the equivalent of 1000 mcg/day or more of fluticasone.

What's more, those taking steroids had a 53-per-cent increase in deaths due to pneumonia within a month of being admitted to hospital.

The Canadians also found that, once the patients stopped taking steroids, their risk of pneumonia decreased.

These findings show that a sharp increase in steroid use-from 13.2 per cent in 1987 to 41.4 per cent just eight years later-may be a contributing factor behind the huge incidence in serious pneumonia cases in the West. Pneumonia is now the third leading cause of hospitalization in the US.

This latest study confirms the findings of earlier research published in the New England Journal of Medicine. In a study of the common prescription combination of inhaled steroids and long-acting beta-agonists compared with a placebo, there was

an increase in pneumonia (of nearly 20 per cent) with fluticasone and with taking it together with the beta-agonist salmeterol (of 18 per cent), compared with a 12-per-cent increase with a placebo.

However, as this was not the objective of the study, it was easy to conclude that the "pneumonia findings were spurious".

Nevertheless, the Canadian data show a link between pneumonia and inhaled steroid use from studies of various design, with different objectives and patient populations. The findings also indicate a clear dose-response relationship between the two.

The Canadian researchers, led by Dr Pierre Ernst, a clinical epidemiologist at McGill, called these findings on the adverse effects of inhaled cortico-steroids "troublesome, given the limited evidence for their efficacy" in patients with COPD.

No doubt Ernst is referring to the years of research carried out by the National Jewish Center for Immu-nology and Respiratory Medicine, in Denver, which found that inflammation is not always present during an asthma attack and, if present, may not respond to steroids.

The conventional view is that the airways become inflamed in severe asthma, which is why they are treated with high doses of steroids.

The Denver research team, which studied 14 patients with severe asthma treated with high doses of oral gluco-corticoid, found that the patients showed no improvement whatsoever with steroids.

They also discovered something else peculiar: each of these asthma patients had an abnormal number of neutrophil cells, the type of white blood cells that the immune system produces to fight off foreign invaders. This suggests that asthma can be viewed as a byproduct of the body's defense mechanism against an allergy (JAMA, 1998; 279: 883).

Lynne McTaggart

Quick and dirty

Long-standing research, often ignored by medicine, shows that inhaled steroids can cause virtually every effect of oral steroids-and very rapidly.

This means that they can:

- decrease bone density, even at doses as low as 400 mg/day (Lancet, 1991; 338: 60-1)

- stunt growth and suppress the adrenal glands (Acta Pediatr, 1993; 82: 636-40; Lancet, 1991; 338: 1535).

- adversely affect a child's cognitive (mental) performance. In one study of visual retention association, six to eight hours after receiving steroids, these children performed significantly worse than the matching controls

(J Asthma, 1986; 23: 291-6)

- cause cataracts and glaucoma, ordinarily only associated with oral steroids (Lancet, 1993; 342: 1306-7)

- thin the skin

- alter fat metabolism.


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