Experts debate whether peanut sensitization can occur through the respiratory tract

PHOENIX — Whether environmental peanut sensitization can occur through the respiratory tract was a matter of debate here at the American Academy of Allergy, Asthma & Immunology Annual Meeting.

Timothy P. Moran, MD, PhD, FAAAAI, associate professor in the department of pediatrics and member of the Center for Environmental Medicine at University of North Carolina School of Medicine, argued that the airway can be a route of peanut sensitization, whereas M. Cecilia Berin, PhD, professor of pediatrics and deputy director of the Jaffe Food Allergy Institute at Icahn School of Medicine at Mount Sinai, countered that sensitization is more likely to occur through the skin, especially given the lack of available peanut aeroallergen in the household.

Respiratory sensitization is possible

One reason why peanut sensitization through the respiratory tract is possible, Moran said, is because peanut protein can be detected readily in the living environment. For instance, studies have shown that dust samples from living rooms, bedrooms and child play areas show median peanut protein levels of 5 µg/g of dust, although it can reach as high as 1,000 µg/g. Also, levels of peanut in house dust directly correlate with peanut sensitization in infants.

“There are these opportunities throughout a child’s life where they can be exposed to peanut that is ubiquitous throughout the environment,” Moran said.

Moreover, Americans spend more than 90% of their lives indoors, and infants in particular spend a lot of time inside, so it’s important to study this indoor “exposome” as it relates to allergy development, he said.

“And, when we’re talking about how you’re being exposed, most people are starting to think now that it’s really nonoral exposure to peanut that is probably the most important factor in whether you become sensitized or tolerant,” Moran added. “One thing I’ve always been fascinated with is that most parents will say it was their child’s first known exposure to peanut when they first had their reaction. This suggests sensitization may have occurred through a nonoral route.”

Moran also noted that anecdotal evidence and case reports have suggested that occupational exposure to inhaled allergens — such as in factories dealing with millet, buckwheat, lupine, egg and shellfish — can result in IgE-mediated food allergy in workers.

Also, other examples exist that prove the point that inhalational exposure to aeroallergens can result in IgE-mediated reactions to foods, such as in pollen-food allergy syndrome and oral mite anaphylaxis.

Phenotyping peanut-specific T cells from humans has showed evidence of initiation of T-cell priming in the airway, Moran said, and peanut-specific T-helper 2 analyses from peanut-allergic patients have expressed high levels of CCR4, which also would imply that they were primed in the lung and not the skin.

Other than this evidence, though, Moran acknowledged that there are not many other in-human trials on this question, as it would not be ethical to expose individuals to inhalant allergens to see if they develop a food allergy.

But mice studies do show that this is a potential path of sensitization, according to Moran, who referred to a study by Dolence and colleagues that showed inhaled peanut flour alone initiated peanut allergy in mice, which was dependent on IL-1 in the lungs and T follicular helper cells playing a critical role in production of peanut-specific IgE.

Moran and colleagues have also conducted studies where they exposed mice to very small amounts of peanut in combination with house dust and they clearly saw an increase in allergic sensitization of the mice. Key factors in house dust that might enable this sensitization are toll-like receptor ligands.

Based on these findings, Moran and colleagues wanted to update the dual allergy exposure hypothesis — involving the skin and GI tract — to also add the airway.

“We agree that the skin is probably a major site of sensitization, particularly in patients with significant eczema,” Moran said. “But we also postulate that it is possible in other patients that airway exposures to peanut in the presence of different environmental adjuvants can also act as a priming site for the development of these peanut-specific T cells that then go on to direct the production of peanut-specific IgE.”

Moreover, there are a lot of children who have peanut allergy and do not have eczema, Moran added.

“It does raise the question of whether it’s possible that exposure through other surfaces besides the skin could also lead to sensitization, such an inhalational exposure,” he said.

Sensitization is likely epicutaneous

Although studies in mice suggest that sensitization through the airway is possible, a lack of aerosolized peanut indicates that this is an unlikely route of sensitization, according to Berin.

For instance, a study by Lovén Björkman and colleagues looking at the airborne amount of peanut that could be detected at difference distances from a source of peanut found that only when the probe was held directly over the source could it detect peanut protein.

“Very rapidly as you got half a meter away, there was a complete drop-off of the availability of peanut that was detectable through the air,” Berin said.

Also, Perry and colleagues took measurements using personal air monitors worn by participants who did various activities such as eat peanut butter sandwiches, shell and consume peanuts, and walk on peanut shells, revealing that under no conditions could peanut protein be detected in the air.

One study by Brough and colleagues did show detectable peanut protein in the air immediately when deshelling peanuts, but the levels dropped off very quickly.

“This suggests that perhaps as an occupational exposure, when directly physically working by deshelling peanut, there is airborne peanut. But in our households, peanut is basically not found,” Berin said.

In addition to the lack of availability of aeroallergen to be breathed in, the timing of sensitization in early life is another argument that would not favor sensitization through the respiratory tract. For instance, a study by Schoos and colleagues looking at patterns of sensitization showed that sensitization to peanut precedes that of aeroallergens.

Given these two arguments against sensitization through the respiratory tract, an alternative hypothesis would be that it occurs through the skin, Berin said.

For instance, Brough and colleagues have shown that peanut antigens linger on surfaces in the house such as on sofa and pillows, and on hands after eating peanut, which could lead to direct cutaneous contact.

Also, eczema has been associated with a greater risk for development of peanut allergy than family history, and eczema in the first years of life is highly associated with peanut allergy.

Patients with peanut allergy have also shown reductions in skin barrier function, as well as alterations in the composition of the skin barrier even in the absence of atopic dermatitis.

Researchers have also found an association between peanut allergy and Staphylococcus aureus colonization on the skin, which might be driven by the presence of type 2 and T follicular helper cells as seen in mouse studies.

“We know that mice can be sensitized either through the respiratory or epicutaneous routes,” Berin said. “It can happen, but does it happen? The argument against that is that the household availability for respiratory exposure is not measurable in house dust, whereas we know it’s retained on the skin, on the sofa and the bedsheets for exposure via the cutaneous route.

“We also know that inflammation of the skin at tissue sites precedes peanut allergy, whereas sensitization to aeroallergens does not generally precede sensitization to peanut,” she added. “Finally, we know there are altered skin barriers associated with peanut allergy shown in the context of the epicutaneous route both by functional measurement and mutations.”

References:

• Berin C. Sensitization to peanut cannot occur through the respiratory tract. Presented at: AAAAI Annual Meeting; Feb. 25-28, 2022; Phoenix (hybrid meeting).
• Brough HA, et al. J Allergy Clin Immunol. 2013;doi:10.1016/j.jaci.2013.02.035.
• Dolence JJ, et al. J Allergy Clin Immunol. 2018;doi:10.1016/j.jaci.2017.11.020.
• Lovén Björkman S, et al. Clin Exp Allergy. 2021;doi:10.1111/cea.13848.
• Moran T. Sensitization to environmental peanut can occur through the respiratory tract. Presented at: AAAAI Annual Meeting; Feb. 25-28, 2022; Phoenix (hybrid meeting).
• Perry TT, et al. J Allergy Clin Immunol. 2004;doi:10.1016/j.jaci.2004.04.009.
• Schoos A-MM, et al. J Allergy Clin Immunol. 2017;doi:10.1016/j.jaci.2017.01.041.
• Sherenian MG, et al. Clin Exp Allergy. 2021;doi:10.1111/cea.13866.
• Smeekens JM, et al. Clin Exp Allergy. 2019;doi:10.1111/cea.13486.
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