COMMEMTARY

Asthma deaths in New Zealand: whodunnit?

Many studies of asthma mortality rely on official registration. The aim of this study was to evaluate the accuracy of death certificates, where asthma was coded as cause of death.

In a 12-month period, medical information on all subjects with asthma officially coded as the underlying cause of death in Denmark, was obtained by reviewing hospital records, contacting general practitioners and sometimes close relatives. A panel of four pulmonologists each examined the obtained information and independently assessed the cause of death.

Of a total of 218 death certificates, 39 were excluded as the cause of death could not be validated. In 16 (9%) of the subjects death from asthma was judged to be the definite cause of death and in 12 (7%) death from asthma was possible. Of 151 non-asthma deaths coded as due to asthma, 109 were judged to have suffered or died from COPD and 14 from heart disease.

The accuracy of Danish death certification in asthma deaths is poor, especially in the elderly, where COPD is often classified as asthma. We conclude that the true asthma mortality in Denmark is substantially lower than officially recorded.

The abundance of health-related statistics routinely collected worldwide invites their misuse from haphazard associations between secular trends of these data. This misuse is often compounded by assessing these associations simply on the basis of a visual inspection of the data. The visual approach to data analysis, known to have several pitfalls, is particularly tempting in the context of asthma where it has often been used. For example, the epidemic of asthma deaths that occurred in New Zealand during the last two decades has been imputed to fenoterol, a medication for asthma, on the basis of a visual assessment of ecological data. The simultaneity of time trends in the asthma death rate and fenoterol market share in that country formed an important part of the statistical basis of the evidence. We verified whether the results of such visual analyses are corroborated by more objective quantitative statistical methods of analysis.

We reanalyzed these same data, namely the time trend data of New Zealand asthma death rates, fenoterol market share, sales of β-agonists and inhaled corticosteroids, measured yearly for the 16-year span 1976–1991, using Poisson weighted loglinear regression. We found that the protective effect of inhaled corticosteroids (rate ratio 0.5 per canister per month; 95% confidence interval 0.4 to 0.7; p = 0.0001) was more closely associated with changes in asthma mortality than either fenoterol (RR 2.7 per canister per month; 95% CI: 0.9 to 7.5; p = 0.06) or all β-agonists combined (RR 1.6; 95% CI: 0.8 to 3.0; p =.19).

We conclude from this quantitative analysis that these ecological asthma mortality data provide evidence of a stronger association with inhaled corticosteroids, little used in New Zealand at the onset of the epidemic but used abundantly at its termination, than with fenoterol. This conclusion is diametrically opposite to that found by the visual approach. The quantitative analysis demonstrates that the visual approach to the analysis of ecological data, although seemingly convincing, can be misleading by creating an optical illusion. This purely visual approach to data analysis may thus have serious implications when the resulting scientific information is used to make vital public health and policy decisions.

The effects of vasoactive drugs, including bronchodilators, on vascular and pulmonary dynamics are interrelated, complex and difficult to measure, but important because of potential deleterious effects on gas exchange.

To assess the effects of fenoterol at both high and low dose on pulmonary gas exchange in 24 hypoxemic patients with stable COPD: fenoterol, 5 mg; fenoterol, 1 mg and ipratropium bromide, 0.5 mg; ipratropium bromide, 0.5 mg; or matched placebo were nebulized in a double-blind, placebo-controlled fashion. Spirometry, ventilation, systemic hemodynamics, and respiratory and inert gases were measured before and 15, 60, and 120 min after each treatment.

Compared with placebo, heart rate (p<0.002) and cardiac output (p=0.05) increased after high-dose fenoterol therapy to return to baseline values by 120 min. Following fenoterol at high dose, mean maximum PaO2 change from baseline decreased by 6.3 ± 1.1 mm Hg (SD) and both alveolar-arterial oxygen pressure difference (P[A-a]O2), by 8.3±4.0 mm Hg, and ventilation-perfusion ( ${\dot{\text{V}}}_{\text{A}}\text{/}\dot{\text{Q}}$) mismatching increased, as evidenced by increments of the dispersion of pulmonary blood flow, without reaching significance; likewise, low-dose fenoterol therapy increased ${\dot{\text{V}}}_{\text{A}}\text{/}\dot{\text{Q}}$ inequalities while both PaO2 and P(A-a)O2 remained unchanged.

In this population of COPD patients, high-dose fenoterol therapy did not significantly increase heart rate and cardiac output resulting in minor adverse consequences on arterial oxygenation and ${\dot{\text{V}}}_{\text{A}}\text{/}\dot{\text{Q}}$ relationships.