Mannino and colleagues did, of
course, study a sample of a normal population,
not subjects selected because
they had worked with cadmium or
had known COPD. The dose-response
relation between cadmium and ventilatory
function was necessarily focused
at low dose levels, and their ability to
demonstrate it undoubtedly owed
much to the great power generated
by so many participants. The relation
could still be causal even if the actual
effect at such low levels of exposure is
minor and not detectable by studies of
smaller populations with higher levels
of exposure.
This assumes that the accumulated
body burden of cadmium (and the more
readily measured urinary excretion of
cadmium) does reasonably reflect the
risk of toxicity from inhaled and
ingested sources alike. This may not be
so. It is interesting that ‘‘doses’’ of zinc
oxide that cause metal fume fever when
inhaled have no comparable effect when
administered by ingestion or intravenous
injection.8 Thus, zinc has to be
inhaled to produce this particular type of toxic reaction. This might explain
why Mannino and colleagues found no
relation between urinary cadmium and
ventilatory function in the never smokers.
The small difference in urinary
excretion levels between the smokers
and never smokers in their study may
consequently be of limited significance.
If there is considerable variability in
metabolic pathways relevant to absorption,
storage, injury, and repair so that
some individuals are particularly susceptible
even at low levels of relevant
exposure, then it is plausible that
cadmium plays at least a contributory
role in the development of smoking
induced emphysema.
Incidentally, cadmium is also recognised
to cause lung cancer …