Changing patterns in asthma morbidity and mortality.

Asthma morbidity and mortality have increased in many countries over the last 10 years or more. In some countries, epidemics of deaths have occurred, while others have shown gradual increases. The New Zealand National Asthma Mortality Study associated mortality with severe asthma, underassessment of severity, undertreatment with corticosteroids, overreliance on bronchodilators, discontinuity of medical care and delay in seeking help. Case-control studies of asthma mortality in New Zealand linked prescription of fenoterol with a higher risk of death from asthma than prescription of salbutamol; this higher risk was not negated by adjustment for markers of severity. A study in Saskatchewan, Canada confirmed the increased risk associated with fenoterol use, but also found a significantly elevated risk associated with salbutamol, especially at higher doses. A randomized, placebo-controlled crossover study of regular versus as-needed beta-agonists undertaken in New Zealand showed increased morbidity from asthma during regular treatment, with increased symptoms, decreased pulmonary function, increased airways responsiveness and overall poorer control of asthma despite constant inhaled corticosteroid treatment. Similar findings were evident in some earlier studies of regular salbutamol. Taken together, several recent studies suggest a deleterious effect of frequent use of inhaled beta-agonists, particularly higher potency preparations. Increased responsiveness to allergen is one possible mechanism for this effect, but whatever the mechanism, frequent use of beta-agonists appears to have caused a shift in the chronic severity of asthma, leading to increased morbidity and mortality.