Allergies are a big problem for a lot of people. If you're someone with pollen allergies, maybe you've wondered how people in the distant past dealt with them. After all, a thousand years ago people mostly worked outside all day, in areas where plants grow well. They had no air purifiers, no allergy medication, and no extra food for people who couldn't work when it was time to plant crops.

The answer is, pollen allergies just weren't very common back then. There was a massive increase in their prevalence from about 1850 to 1950. Here's a paper noting that.

the hygiene hypothesis

That paper argues that the increase in allergy prevalence is due to increased hygiene. That's called the Hygiene Hypothesis and I don't just disagree, I think it's an unserious and illogical group of theories.

First, let's keep in mind the basics of how the immune system works. An immune response to some target develops when the target is present at the same time & place as harm or a known-harmful substance. Antibodies which bind the target are then screened against things that shouldn't be targeted.

Now then, the Hygiene Hypothesis refers to several things that use the same name despite being different. I don't like spending my time on theories where people can't make up their mind about what they mean and pick a name referring specifically to that, but I guess I'm obligated to here. That Wikipedia article includes:

1. Insufficient activation of the TH1 arm would stimulate the cell defense of the immune system and lead to an overactive TH2 arm, stimulating the antibody-mediated immunity of the immune systems, which in turn led to allergic disease. However, this explanation cannot explain the rise in incidence...

2. North South Gradient seen in the prevalence of multiple sclerosis has been found to be inversely related to the global distribution of parasitic infection.

3. An alternative explanation is that the developing immune system must receive stimuli (from infectious agents, symbiotic bacteria, or parasites) to adequately develop regulatory T cells.

About (1), it's not like immune systems have a quota of things to become sensitive to. There has to be a reason for a person developing an immune reaction to a particular thing. If it was random up to a quota, people wouldn't be able to live at all. This does nothing to explain why people have started developing allergies to specific things of specific types.

About (2), you really can't explain allergies as not-having-parasites. There are many different parasites, they're in specific geographic areas, and they have different effects. They don't correlate well with the history of allergies if you actually consider details and aren't just p-hacking.

About (3), it's not as if people developing pollen allergies are all people exposed to hardly any bacteria. It's not as if, their immune system being stimulated by an initial pollen allergy, they don't develop other pollen allergies. Also, that's just not how the immune system works.

Further, compared to societies 1000 years ago, population density today is much higher, and there's rapid global travel. Diseases like COVID can spread quickly, many young kids go to daycare where they catch diseases constantly, older kids go to classes, people spend more time indoors, there's public transit, etc etc. While people today are much less likely to get sick from contaminated water or lack of hand-washing, there's still plenty of exposure to infectious diseases.

The Wikipedia article includes a few other criticisms, despite articles on a particular theory tending to favor that theory because of how editor interest works. For example:

The hygiene hypothesis has difficulty explaining why allergic diseases also occur in less affluent regions. Additionally, exposure to some microbial species actually increases future susceptibility to disease instead, as in the case of infection with rhinovirus (the main source of the common cold) which increases the risk of asthma.

a note about references

Why would I trust a paper I linked about one thing, and not about another thing? No, that's not what I'm doing.

Generally, when I link to papers, it's not that I based my opinion on those papers; it's that I already knew the relevant answer for some reason and found some convenient sources that I mostly agree with the relevant parts of. You should take them as "this is what I mean, and some evidence for it" rather than "this is why I believe this is true". In this case, I found something that also talked about the Hygiene Hypothesis, because it seemed necessary to mention that.

Sure, that means my selections could be biased, but that could be the case anyway. You shouldn't just trust the references in blog posts; you should do your own searches in case they're bad. I'm sure I could find 10 papers saying global warming is fake; doesn't mean that's correct.

In my view, you can't trust someone who, not knowing something, just finds a scientific paper and goes with whatever it says. Before saying "this is correct", you need multiple sources and some understanding of a plausible mechanism and cross-referenced info from multiple fields, at the very minimum.

air pollution

OK then, something changed that caused an increase in allergies, and I don't think it was better sanitation, so what was it? I think it's interaction between pollen grains and air pollution.

The obvious potential ways pollen could interact with pollution are:

• electrostatic adhesion of particulates
• van der Waals adhesion of PAHs
• reaction with ozone, nitrogen oxides, or sulfur oxides
• reaction with formaldehyde

The connection of pollen allergies and air pollution has been studied some. This paper says:

The results of this study showed that ozone in particular had an impact on the symptom severity of pollen allergy sufferers. Elevated ozone concentrations significantly increased the symptoms of allergic rhinitis in the pollen-allergic patients during the periods of birch, grass, and ragweed pollen flight (model A).

However, these results are not intended to show that other air pollutants are harmless to pollen allergy sufferers. In Vienna, nitrogen dioxide and sulfur dioxide concentrations very rarely exceed the threshold value. Particulate matter is definitely measured in elevated concentrations, but the concentration peaks are in winter and thus outside the three analyzed pollen seasons.

This paper says:

Chehregani et al. confirmed the accumulation of sub-micronic particles on the surface of Zinnia elegans pollen grown in the presence of pollutants, which resulted in an increase in allergen release into the environment and increased pollen allergenicity (13).

Armentia et al. compared the allergenicity of samples gathered from different areas during the pollination period and found the in vitro and in vivo allergenicity of grass pollen was greater in urban than in rural areas (22). In addition, in skin prick tests, the in vivo allergenicity of Cupressus arizonica pollen extracts was greater from polluted than from unpolluted sites. (17). Also, in vitro allergenicity of Ambrosia artemisifolia pollen grown near heavy traffic was greater than that of pollen from rural districts as measured by Ghiani et al., using IgE reactivity of sera from people sensitized to this pollen

It was found that that NO2, a major traffic-related air pollutant, enhanced the allergenicity of Bet v 1a and its affinity for IgE through the formation of nitrotyrosine residues.

food allergies?

The increase in food allergy rates seems to have come later than the increase in pollen allergies, so it seems likely that there's a different mechanism involved. I have some thoughts on that but they're beyond the scope of this post.

can this be solved?

Everyone knows antihistamines, which are cheap and widely used. But some people overestimate what antihistamines do about allergies. They reduce the downstream effects of an immune response, but they don't prevent the immune response itself. They also only act on a few receptors, while immune responses involve hundreds of signaling molecules and receptors, so obviously they're not a "cure for allergies", just a mitigation of some symptoms.

As for reducing the actual immune response to allergens, omalizumab is a drug that's sold now, but it's basically a general immunosuppressant, and being a monoclonal antibody it's rather expensive.

The immune system uses molecular tags to mark molecules as targets. It also has tags that indicate things should not be targets. In theory, it's possible to use that to cure specific allergies in a selective way. This paper says:

Here we show that established antigen-specific responses in effector T cells and memory T cells can be suppressed by a polymer glycosylated with N-acetylgalactosamine (pGal) and conjugated to the antigen via a self-immolative linker that allows for the dissociation of the antigen on endocytosis and its presentation in the immunoregulatory environment. We show that pGal–antigen therapy induces antigen-specific tolerance in a mouse model

"Determining a target of someone's immune system and getting their immune system to stop targeting it" can be compared with the opposite, "determining something that a person's immune system should attack and getting their immune system to attack it". There are different levels of difficulty here:

• Current monoclonal antibodies target some known antigen. They're the same for all patients and still very expensive.
• If you can find person-specific antigens to target, and design new antibodies which bind to those but not normal human proteins, that brings you to individualized cancer vaccines, which I also wrote a post about.
• Allergy treatments would then be somewhere between those in difficulty: you need to find and isolate/produce the relevant allergen (to a particular patient) from eg a pollen, and produce an individualized treatment using that. But you don't need to design selectively binding antibodies.

Of course, curing a cancer is considered higher-value than curing an allergy, and research funding is distributed accordingly. There are also severe autoimmune diseases, but they're less common than cancer in general.

conclusion

Now that (thanks to my blog post here) everyone finally knows air pollution is bad, we can simply minimize and avoid it. You're welcome.

More seriously, I do have several proposals for reducing air pollution, not that industry leaders or government officials are likely to be interested. For example:

• Here's a post I wrote about particulate pollution, where I proposed using cermet car brakes made of pure iron filled with MgO particles.
• Tires use carbon nanoparticle "reinforcement", and those particles are released by tire wear. I know of some ways to make precipitated CaCO3 nanoparticles with suitable properties for tires, that should give performance at least as good as carbon particles.
• changing VOC regulations

In the meantime, I suppose more people should get an air purifier.