Thursday, May 12, 2016

Sneezin' All Season

Notice that not one person is covering their mouth 
and nose here. Makes for better video, 
but still…..gross.
The spring allergy season is back with a vengeance. Many of your friends and loved ones are sneezing, looking as if someone killed their dog, and stuffing facial tissues in their pockets and purses like they were fifty dollar bills. Despite the TV commercials that suggest otherwise, people don’t get that upset with other people’s sneezing, unless they neglect to cover their nose and mouth, in which case they deserve all the ridicule that can be heaped upon them. However, it makes one wonder what exactly is going on inside them that causes them to sneeze, and how does that sneeze play out biologically? Now there’s an interesting story.

A sneeze is the body’s way of trying to expel foreign material that is irritating the respiratory system, most likely the very upper respiratory system – the nasal passages. In the case of spring allergies, the offender is most likely to be grains of pollen. The rhinitis (rhino = nose, and -itis = inflammation) caused by seasonal allergens (hay fever to you and me) are small particles that stimulate an immune response for some reason. In almost all cases they are not harmful particles, as is the case with pollen grains, except that some can induce very strong allergic responses. So why do some people’s bodies try so hard to expel them?

An allergen is nothing more than a protein or carbohydrate, some sort of biomolecule, that your body recognizes as foreign and against which it mounts a specific immune response. For most people, any one specific particle may be seen as foreign, but your body doesn’t go crazy over it; it has been tolerized (learned not to respond), or the response is held in check by other parts of the immune system. But for those unlucky few (or many), pollen grains are a type of allergen that stimulates a large IgE (one type of antibody) response, along with chemicals like histamine and leukotrienes.

The reasons that some people develop an allergic rhinitis to one or more materials aren’t completely known. There is some evidence that if you are fighting off a viral infection and at the same time are first exposed to the allergen, then the heightened activity of the immune system will stimulate a response to the innocuous material. And once that happens, you’re sunk. The body has an immune memory; it builds a small army of cells that then recognize that particular allergen, and if it enters the body again, a strong response will follow and an additional memory response will be built.

Goldenrod has a bad reputation as an autumn allergen. In
truth, it is an insect pollinated plant, so it is not carried by
the wind and snorted as an allergen. Look, she’s not
sneezing. The problem is all the ragweed that grows near
the goldenrod – it’s wind-pollinated.
Therefore, some people believe that too much exposure to viruses and bacteria and other foreign materials when very young will lead to more allergies (there is a genetic component that makes some people more susceptible, but that is too big a topic for us here). On the other hand, many scientists believe that the opposite situation is just as bad or worse for developing allergies. If an environment is too clean, then children are very likely to develop food, seasonal, and perennial allergies. This is called the hygiene hypothesis, and most researchers accept it as true, even if we aren't quite sure of its mechanisms yet.

It may be that too little exposure to bacteria and viruses (which stimulate more a type of immune response called Th1) actually makes the body more likely to go overboard when an antigen stimulates a Th2 response (the type of response induced by allergens). There needs to be a balance between Th1 and Th2 that helps keep them both from over-reacting. It is also possible that when babies are very young, before they have had time to develop their own adaptive immune system (build on their own by being exposed), it is important to stimulate their innate immune system (always on guard and doesn’t require learning to react). The innate response helps build the adaptive system and works to balance the adaptive Th1 and Th2 responses.

It is no coincidence that farmers’ kids have fewer food and
environmental allergies. They are exposed to more
arabinogalactan, which scientists think this is one of the
antigens that teaches the Th1 and Th2 systems to balance
and dampens their response so body doesn’t over react to
foreign molecules and develop allergic responses
and memory response.
Finally, the hygiene hypothesis of allergy development may be mediated by a lack of early childhood allergen and germ exposure which prevents the development of a regulatory immune response. Regulatory immune cells are stimulated each time an immune response is generated; they work to tone down the response and finally turn it off. If not exposed often enough to foreign materials when young, many kids these days don’t develop the regulatory system that would keep the Th2 response to allergens in check. Think about it, hyper-clean environments with HEPA filtered air conditioners and vacuum cleaners, antibacterial soaps, surface and toys, the fact that kids just don’t play outside much anymore. These could all lead to more allergies just because their bodies haven’t learned to handle foreign molecules well.

In terms of seasonal allergic rhinitis, the allergens we are talking about most often are pollen grains. Many plants are fertilized by insects; the insect comes to a flower to drink nectar, the pollen sticks to them, and when they get to the next flower, the pollen is transferred to the stigma and the male gamete cells grow out of the pollen grain via the pollen tubules, down to the ova and fertilized the egg. However, that isn’t the only way pollen grains can be dispersed to other plants; the wind often plays a role. Wind-pollinated plants have small pollen grains, light enough that they will be spread far and wide by a gentle breeze. Unfortunately, this is rather hit or miss; they aren't going to be blown directly to another plant of the same species (as a bee would carry them to the next flower). Since the chances of a single pollen grain finding a flower are low, the plant has to make millions of times more pollen grains. That is a problem for people who suffer seasonal allergies.

Iguanas, especially marine iguanas, sneeze more than any
other animal. The sneezing is a way for the to expel certain
salts that are a byproduct of their digestive process.
There is just so much pollen in the air, the chances of coming across some each day of the season are so high as to be inevitable. Many plants take advantage of the spring increases in temperature, sunlight, and water to do their reproduction, so there is a lot of pollen around in the springtime. Other plants reproduce in the fall, so seasonal allergies come back then, although the offending pollen types will be different from spring to fall. The pollen is in the air, you breathe in the pollen, and it gets stuck in the mucus of your nasal passages. This prevents it from getting to your lungs, but your body still wants to get rid of it. So how does your body know it is there and then trigger a sneeze?

Immune cells are always on the prowl for foreign invaders, especially in/on parts of the body that contact the outside world. Your nose qualifies as such, so there are many immune cells  patrolling your nasal passages that recognize specific antigens. When an immune cell meets that one antigen (or maybe two if there is a cross reaction) that it is built to recognize, it triggers a response. In the case of allergic rhinitis, the responses are to release an antibody type called IgE. The IgE then binds to other immune cells, like eosinophils and mast cells, and then release histamine and leukotrienes, amongst other things. The histamine makes your nose and eyes itch. The chemicals make the small blood vessels leaky, so fluid comes out making your eyes water and your nose run. They stimulate more mucus production, so you get congested. Blech! In addition, the histmaine and leukotrienes do one more thing, they stimulate nerve endings in your nose to trigger a sneeze. The sneeze is meant to get those allergens out of your system as quickly and forcefully as possible.

Contrary to popular belief, your eyes won’t pop out if you
sneeze with while they are open. The blood pressure does
tend to rise fractionally behind your eyes when sneezing,
but it isn’t enough to make them bulge, let alone pop out.
The reasons that the reflex closes your eyes is to avoid
having infected mucus or saliva fly into them and to protect
them during your wild head movement when sneezing.
The nerve impulse travels to your brain, a part called the medulla, and this triggers a constriction of your intercostal chest muscles, your diaphragm, and your abdominals. You inhale, and the constriction of the palate and larynx then holds the air in your lungs as your chest and abdominal muscles start to contract. This builds up pressure, until the throat opens and the air comes rushing out at 70-100 mph. A sneeze can travel 12-20 feet and can carry 40,000 droplets of saliva and mucus. This is: 1) very good for expelling allergenic particles in the nose and throat, and 2) not something anyone wants to share with you, so cover your mouth and nose – preferably in the crook of your elbow in case you plan on opening any doors or shaking hands soon.

There is another reason why a sneeze might be in order during allergy time. A 2012 study showed that the mechanism to get rid of mucus (called the muciliary elevator) sometimes get stalled when mucus is overproduced and full of particles. The clearance mechanism uses the rhythmic beating of cilia on the nasal cells to brush the mucus toward the mouth to be coughed out or swallowed. The researchers used some nasal tissue and sent a pressure wave over the cells to mimic a sneeze. The pressure wave stimulated the cells to start clearing mucus by beating their cilia, so the scientists describe a sneeze as a rebooting of the mucus clearing mechanism. Unfortunately, people with chronic sinusitis and chronic allergies have nasal passage tissues that don’t reboot, so they just keep sneezing and sneezing without any relief. In the case of people with allergies, antihistamines and decongestants are a savior. For everyone else, just sneeze and be done with it – don’t self-medicate at the drop of a hat, people take too many drugs.

Dogfish Head 90 Minute Imperial IPA is one of the beers
that is famous for making people, those who are susceptible,
sneeze. Fermented beverages are high in histamine, and this
may be a reason for the sneezing. Or perhaps it could be an
allergy to the boiled form of alpha acids from hops;
iso-alpha acids like humulone.
More interestingly, people can sneeze for non-allergic reasons. The immune response to a cold virus produces the same chemicals and sneeze response, while pulling at your eyebrows or tweezing them stimulates the same nerve that innervates your nasal passages so you might sneeze then as well. But there are weirder reasons. Some people, called photics, sneeze in response to sudden onset of a bright light. This is a genetic trait and involves higher brain centers, like the visual cortex. Therefore, it is a reflex that extends beyond the brainstem or spinal cord – very weird. It is called, for obvious reasons, ACHOOs (Autosomal Dominant Compelling Helio-Opththalmic Outburst syndrome). Other people suffer from snatiation –sneezing when their bellies are full. This is also genetic and is inherited as an autosomal dominant trait. And some people have a tendency to sneeze after being intimate. The weirdest? Sneezing with hoppy beers – but that’s another story.

Contributed by
Mark E. Lasbury, MS, MSEd, PhD
As Many Exceptions As Rules

Zhao, K., Cowan, A., Lee, R., Goldstein, N., Droguett, K., Chen, B., Zheng, C., Villalon, M., Palmer, J., Kreindler, J., & Cohen, N. (2012). Molecular modulation of airway epithelial ciliary response to sneezing The FASEB Journal, 26 (8), 3178-3187 DOI: 10.1096/fj.11-202184

Teebi AS, & al-Saleh QA (1989). Autosomal dominant sneezing disorder provoked by fullness of stomach. Journal of medical genetics, 26 (8), 539-40 PMID: 2769729

Takubo M, Inoue T, Jiang S, Tsumuro T, Ueda Y, Yatsuzuka R, Segawa S, Watari J, & Kamei C (2006). Effects of hop extracts on nasal rubbing and sneezing in BALB/c mice. Biological & pharmaceutical bulletin, 29 (4), 689-92 PMID: 16595900

Langer, N., Beeli, G., & Jäncke, L. (2010). When the Sun Prickles Your Nose: An EEG Study Identifying Neural Bases of Photic Sneezing PLoS ONE, 5 (2) DOI: 10.1371/journal.pone.0009208

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