Acute eosinophilic pneumonia (AEP) is an
acute febrile illness that can result in life-threatening
respiratory failure. Mechanisms are unclear, but the
association with new-onset smoking suggests a possible
link (1). Because it may be mistaken for other
diseases, especially severe community-acquired
pneumonia, the diagnosis may be missed or delayed
(2). We report a case of a female patient who developed
AEP after recent onset of smoking and extensive
unprotected exposure to glyphosate-surfactant.
Four years later, during similar circumstances, she
was exposed a second time to the same toxic agent,
causing a clinical relapse.
...
An thorough exposure history revealed that a few
days before the onset of symptoms the patient had
helped for at least six hours to clean up the school yard
of her daughter using large amount of herbicides containing
glyphosate-surfactant (Roundup, probably
41% glyphosate isopropylamine + 15.4% polyoxyethyleneamine
(POEA)). It happened to be a nice warm day, she used the herbicide
without any protection. Moreover, she restarted smoking three weeks before
this first episode of exposure to glyphosate-surfactant.
...
Additionally, cytochrome P450 (CYP) genotyping
revealed a heterozygous CYP2C19 (*1/*2) and
no polymorphisms in the CYP2D6 and CYP2C9
genes. The *1 allele of the CYP2C19 gene codes for
a fully functional enzyme, but the *2 produces an enzyme
with decreased function resulting in an overall
lower enzymatic activity or a so-called intermediate
metabolizer.
Glyphosate-based herbicides are worldwide and
extensively used to eliminate weeds. Most
glyphosate-based products contain a surfactant
which helps glyphosate to penetrate plant cells. In
vitro studies evaluating glyphosate in human primary
cells and cell lines show that the cytotoxicity of
commercial formulations of glyphosate, containing
the surfactant POEA, is much higher than the active
component itself (4-7). This might lead to an underestimation
of the toxicity of glyphosate-based
herbicides compared to the active component
glyphosate only.
...
major xenobiotic-metabolizing enzymes was measured
in human hepatic microsomes, glyphosate was
shown to be a potent inhibitor of CYP2C9 (and
CYP2C8) but it did not inhibit CYP2C19 and
CYP2D6 (14). Since the mechanisms of chemicals
like pesticides are comparable to drugs, drug-induced
ILD could be expanded to xenobiotic-induced
ILD (13).
...
This case highlights the
importance of a thorough exposure history e.g., possible
occupational and environmental exposures together
with drug-intake. Genotyping should be considered
in cases of severe unexplained pulmonary
damage. It also warrants further research to investigate
to which degree toxicity of glyphosate-surfactant
might be associated with reduced metabolic capacity
of CYP enzymes.
