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My old website can be found at www.stevecarper.com/li I am no longer updating the site, so there will be dead links. The static information provided by me is still sound.

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Tuesday, February 26, 2008

Allegic Reactions from Lactose in Dry Powder Asthma Inhalers

A discussion on the No Milk List raised the perennial question of whether allergic reactions could occur when people are exposed to pharmaceutical grade lactose, the kind used in hundreds of prescription and OTC medications as a filler and binder.

Very little is in the medical literature about this. I'm grateful to Tammy Powell of the NIH, who 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/PIIS0091674902819248.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/PIIS0091674903026770.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/PIIS0091674905031015.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.

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2 comments:

Anonymous said...

Here's another reference for allergic reactions to lactose:

Allergic skin reactivity and chemical properties of allergens in two grades of lactose.
Author(s): Kaminogawa, S, Kumagai, Y, Yamauchi, K, Iwasaki, E, Mukoyama, T, Baba, M
Source: Journal of Food Science Volume: 49 Issue: 2 Pages: 529-530, 535 Published: 1984

Abstract: Skin tests of the nondialysable fraction of lactose were performed on patients with a clinical diagnosis of cow's milk allergy. Yields of brownish-coloured residue allergens (ALG), were 0.006% from reagent grade lactose (ALG 1) and 0.011% from lactose used in a commercial infant food formula (ALG 2). The ALG was separated into 4 fractions by chromatography on Sephadex G-75. Highest incidences of positive skin reaction among the 4 ALG 1 and ALG 2 fractions were 8/9 and 8/12 resp. ALG fractions were identified as a sugar protein complex and the protein moiety of ALG contained high amounts of glutamic acid (or glutamine), threonine, asparagic acid (or asparagine) and proline.
Accession Number: 1984-09-L?0649
Document Type: Journal Article
Language of Text: English
Address: Dep. of Agric. Chem., Univ. of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113, Japan

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