National pholcodine consumption and prevalence of IgE-sensitization: a multicentre study.
BACKGROUND
The aim of this study was to test, on a multinational level, the pholcodine (PHO) hypothesis, i.e. that the consumption of PHO-containing cough mixtures could cause higher prevalence of IgE antibodies to PHO, morphine (MOR) and suxamethonium (SUX). As a consequence the risk of anaphylaxis to neuromuscular blocking agents (NMBA) will be increased.


METHODS
National PHO consumptions were derived from the United Nations International Narcotics Control Board (INCB) database. IgE and IgE antibodies to PHO, MOR, SUX and P-aminophenyl-phosphoryl choline (PAPPC) were measured in sera from atopic individuals, defined by a positive Phadiatop test (>0.35 kU(A)/l), collected in nine countries representing high and low PHO-consuming nations.


RESULTS
There was a significant positive association between PHO consumption and prevalences of IgE-sensitization to PHO and MOR, but not to SUX and PAPPC, as calculated both by exposure group comparisons and linear regression analysis. The Netherlands and the USA, did not have PHO-containing drugs on the markets, although the former had a considerable PHO consumption. Both countries had high figures of IgE-sensitization.


CONCLUSIONS
This international prevalence study lends additional support to the PHO hypothesis and, consequently, that continued use of drugs containing this substance should be seriously questioned. The results also indicate that other, yet unknown, substances may lead to IgE-sensitization towards NMBAs.
Department of Clinical Immunology and Transfusion Medicine, Karolinska University Hospital, Stockholm, Sweden.
S G O
SG
Johansson
E
E
Florvaag
H
H
Oman
L K
LK
Poulsen
P M
PM
Mertes
N J N
NJ
Harper
L H
LH
Garvey
R
R
Gerth van Wijk
T
T
Metso
A
A
Irgens
T
T
Dybendal
J
J
Halsey
S L
SL
Seneviratne
A B
AB
Guttormsen
D000707:Anaphylaxis / Q000453:epidemiology / Q000276:immunology; D000996:Antitussive Agents / Q000276:immunology*; D003061:Codeine / Q000031:analogs & derivatives* / Q000276:immunology; D003429:Cross Reactions; D004342:Drug Hypersensitivity / Q000453:epidemiology / Q000276:immunology; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood* / Q000276:immunology; D009020:Morphine / Q000276:immunology; D009025:Morpholines / Q000276:immunology*; D009465:Neuromuscular Agents / Q000009:adverse effects / Q000276:immunology; D010767:Phosphorylcholine / Q000031:analogs & derivatives / Q000276:immunology; D015995:Prevalence; D000644:Quaternary Ammonium Compounds / Q000276:immunology; D013390:Succinylcholine / Q000276:immunology
D000996:Antitussive Agents; D009025:Morpholines; D009465:Neuromuscular Agents; D000644:Quaternary Ammonium Compounds; C088774:4-aminophenylphosphorylcholine; D010767:Phosphorylcholine; D007073:Immunoglobulin E; D009020:Morphine; D013390:Succinylcholine; C008872:pholcodine; D003061:Codeine