Tammy Powell of the NIH sent me some cites on the possibility of allergic
reactions to dry powder inhalers containing lactose. I've done some further
searching.
In the abstracts section of J Allergy Clin Immunol (2002, 109(1); S259), Anna
H Nowak-Wegrzyn et al. state that "To our knowledge, the issue of
pharmaceutical grade lactose as a source of potential milk contamination has not been
studied." They therefore tested "samples from two different lots of each:
Serevent TM Discus ®, Advair TM Discus ~ (100/50, 250/50, 500/50), Flovent TM
Rotadisc ® (GlaxoSmithCline), and Foradil TM Aeroliser ® (Novartis). Milk proteins
were detected in all tested DPIs. Whey proteins were present at much higher
concentrations than casein or whole milk protein, consistent with the method of
lactose purification."
http://download.journals.elsevierhealth.com/pdfs/journals/0091-6749/PIIS009167
4902819248.pdf
In 2004 Nowak-Wegryzn and her team published a letter to the editor (2004;
113(3): 558-60) about an actual case, that of an eight-year-boy.
http://download.journals.elsevierhealth.com/pdfs/journals/0091-6749/PIIS009167
4903026770.pdf
"The patient continued to receive Advair for several months without any
adverse reactions and with excellent asthma control. However, after inhalation of
three consecutive doses from a new diskus, he immediately complained of chest
tightness and feeling of distress that were treated with oral diphenhydramine
and inhaled bronchodilator at home." Caseins were detected in samples from the
Advair.
They further looked into whether this was an isolated incident or a general
problem. The results were mixed, for a variety of reasons.
"Another factor that may contribute to lower threshold for inhaled food
allergens is that allergenicity of milk proteins may be enhanced by formation of
the lactose-protein complexes. Nonenzymatic glycosylation of milk proteins
occurs during heat treatment (Maillard reaction), leading to significant changes in
the 3-dimensional structure of these proteins. These conformational
modifications might lead to large glycoprotein complex formation and enhanced
allergenicity. In fact, intradermal skin test reactivity to â-lactoglobulin–lactose
conjugates has been shown to be 10- to 100-fold increased compared with native
â-lactoglobulin.9 Furthermore, large complexes may be randomly distributed
explaining why some lots of Advair contained larger amounts of milk proteins
compared with others. In addition, the purity of lactose USP may differ among the
manufacturers as well as among the batches from the same source. A recent paper
reported that none of the 24 children with well-characterized immediate cow’s
milk allergy reacted on a blinded challenge with soy-based infant formula
containing lactose and that there was no detectable milk protein in a single batch
of lactose provided by an Italian manufacturer."
A second clinical case, that of an adult, was reported in the abstracts
section of that journal in 2006 (117(2); S95). A dry inhaler powder was the cause,
but there is too little information to be useful otherwise.
http://download.journals.elsevierhealth.com/pdfs/journals/0091-6749/PIIS009167
4905031015.pdf
A comment on the 2004 letter can be found in the Jan. 1, 2005 issue of Child
Health Alert.
http://www.accessmylibrary.com/coms2/summary_0286-18598172_ITM
"COMMENT: This well-documented report indicates that parents can be
legitimately concerned about milk protein contamination in lactose-containing
medications. How often this might create a problem is quite another matter. In the case
reported above, the child was so allergic to milk protein that he previously
even had reactions to tiny amounts of milk protein that came in contact with
his skin. It may be that this highly allergic child used a product that just
happened to be highly contaminated with milk protein, and this coincidence might
be so rare that it would be unlikely to happen to another child. However, for
a child who has a severe sensitivity to milk protein, it is important to know
that lactose in a medication can indeed contain small amounts of milk
protein."
I'd suggest that these reports be viewed with great caution. The boy was one
of those rare, extremely sensitive individuals who reacted even to skin
contact with milk protein. It's hard to tell from reading the report whether
contamination occurred in the batch he reacted to, whether procedures changed at the
factory, or whether other factors might have led to a reaction when there
normally wouldn't be one.
An allergic reaction to lactose is a concern, but few even of those who are
dairy allergic have to be specifically concerned. I still haven't found any
analyses of potential reactions from swallowing lactose as opposed to dry powder
inhalers.
I'm always torn between dismissing odd single-source reports and considering
them as tips of icebergs of under-reported problems. You'll want to decide
which way to lean for yourselves.
I'm also putting this report up on my Planet Lactose blog to see what
reactions, pun intended, it gets there.
http://planetlactose.blogspot.com/
Steve Carper
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