Potential Benefits of Thumb-sucking and Nail-biting in a Too-Clean World

In a world of Lysol and Purell, it's easy to become all-consumed with keeping clean. And why not? We're on the go more than ever now:  we're working longer hours (1, 2), spending more time commuting (3), and we’re under constant pressure to keep up to date on all the available social media networks (4). No one has time to be slowed down with the flu or a cold. So we dab on a little hand sanitizer before we eat, clean our houses regularly with bleach-containing products, and hold our breath when someone sneezes in a crowded elevator (or maybe that's just me).

But is there such a thing as being too clean? Researchers who are focused on testing this so-called "hygiene hypothesis" think there may be.

 

The hygiene hypothesis proposes that living in a germ-free world is disadvantageous to our health. Studies testing the hygiene hypothesis have shown correlations between our squeaky-clean developed societies and increases in allergic conditions, compared to developing societies lacking modern infrastructures that support public health (5, 6). Some studies even point to differences in the levels of allergic conditions in cities versus rural towns within the same country (7). While such studies only suggest correlations, and don't definitively show clean environments cause a predisposition to allergies, their findings are worth considering.

While the biological explanation for the hygiene hypothesis is still being studied, evidence from such studies so far suggests that when our immune systems aren't regularly challenged by germs normally present in the environments we've been co-evolving with for millennia, the result is an immune system that is predisposed to allergic reactions. Our immune systems rely on a series of specialized cells programmed and primed to respond to different pathogenic and environmental challenges in a coordinated fashion:  for example, some cells respond to bacteria and viruses while others respond to parasites. Researchers investigating biological explanations for the hygiene hypothesis have proposed that a lack of exposure to bacteria and viruses in childhood causes a shift in the population of immune cells away from cells primed and ready to attack those germs and instead toward a population of cells programed to respond to allergic stimuli (6).

Of course being clean is a good thing. An awareness of how diseases spread and how to take precautions against them is one of the reasons why modern society has been able to flourish. Hand washing and sterilization techniques introduced in the 1800s by Dr. Ignaz Semmelweis dramatically reduced a common cause of death in maternity wards (9). Modern epidemiology enables us to learn and track how certain diseases can be spread (including the recent outbreak of E. coli in flour) so we can take preventative measures to avoid further spread of diseases. We're careful to cook our food thoroughly to avoid food borne illnesses like salmonellosis. All of these behaviors protect us from unwanted illnesses, and allow us to carry on with our lives. While we certainly don't want to undo all of the advances we've made in limiting the spread of disease, evidence suggests that there needs to be a balance between being too dirty and too clean.

A line of souvenirs at Disney parks last summer included hand sanitizers featuring popular kids characters. Image from https://disneyparks.disney.go.com/blog/2015/08/summer-of-souvenirs-continues-with-new-items-at-disney-parks/

For example, it was recently published in the journal Pediatrics (8) that thumb-sucking and nail-biting, generally thought of as being unsanitary, may help children avoid developing environmental allergies. The results came out of the Dunedin Multidisciplinary Study, in which researchers followed over 1,000 children born in Dunedin, New Zealand between 1972 and 1973 throughout adulthood. For this particular question, children were first examined at ages 5, 7, 9, and 11 and then tested for certain allergies at 13 and 32 years of age. The researchers conducting this study, Stephanie Lynch and Dr. Robert Hancox (from the University of Otago, New Zealand), and Dr. Malcolm Sears (McMaster University and St Joseph’s Healthcare, Ontario, Canada), found that the individuals who had been frequent thumb-suckers or nail-biters as children tested positive for allergic sensitivities less often than those who had not frequently engaged in those habits. More specifically, the researchers report that 49% of participants who had not been frequent thumb-suckers or nail-biters had positivity allergy tests, whereas only 31% of participants who had sucked their thumbs and bit their nails as young children had positive allergy tests. 

Granted, this is only one study and it's still probably not a good idea to advocate for children keeping their dirty hands in their mouths all of the time. After all, no one wants their child to be sick. But perhaps thumb-sucking is one thing parents don't have to worry about so much after all. Perhaps instead, we can trust that our bodies are designed to deal with those little germ and dirt exposures, and maybe even benefit from them in the long run.

http://peanuts.wikia.com/wiki/%22Pig-Pen%22

Contributed by:  Kelly Hallstrom

Follow Kelly on Twitter.

1. http://abcnews.go.com/US/story?id=93604&page=1

2. https://www.theguardian.com/business/2016/mar/27/britons-working-longer-hours-with-no-gain-in-productivity-study-finds

3. https://www.washingtonpost.com/news/wonk/wp/2016/02/25/how-much-of-your-life-youre-wasting-on-your-commute/

4. http://www.dummies.com/how-to/content/ways-to-stay-uptodate-with-social-media-changes.html

5. http://www.ncbi.nlm.nih.gov/pubmed/9643741

6. http://www.ncbi.nlm.nih.gov/pubmed/11964470

7. http://www.ncbi.nlm.nih.gov/pubmed/9228959

8. http://pediatrics.aappublications.org/content/early/2016/07/07/peds.2016-0443

9. http://www.npr.org/sections/health-shots/2015/01/12/375663920/the-doctor-who-championed-hand-washing-and-saved-women-s-lives

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

Complexities Of Allergic Disease

Last time we discussed the main players involved in the immune response to allergens, in the reaction called Type I hypersensitivity. We know that hay fever and other allergies are a result of atopy, the genetic predisposition to mount excessive IgE-mediated immune responses. Atopy is derived from a Greek word that means unusual or out-of-place. Although the immune overreaction is indeed out of place, the prevalence of allergic disease in society is not. Approximately 25% of the world’s population suffers from allergies, making it one of the most common chronic diseases. Unfortunately, this number is actually increasing, so researchers are trying to understand the factors that contribute to allergic disease.

Advances in genome sequencing and the completion of the Human Genome Project have allowed scientists to use genome-wide association studies (GWAS) in attempts to identify certain disease-causing genes. While many candidate genes have been described for hay fever, each search appears to reveal additional candidates. It has become clear that hay fever is a complex disease, driven by genetics and environmental exposures, both pre- and postnatal. Because of this complexity, atopy does not follow a Mendelian model of inheritance, like eye or hair color.

To perform GWAS, researchers collect blood or tissue samples from individuals with the disease of interest and from symptom-free control subjects. In many allergy studies, the controls are within the same family, which helps tease apart genetic differences that might actually contribute to disease. This is helpful because 300,000 to 1 million changes in the DNA are tested. These changes called single nucleotide polymorphisms (SNPs), a type of mutation that indicates a single change in the DNA base pair. If certain SNPs appear more frequently in the individuals with the disease, they are said to be associated with that disease. Additional DNA sequencing is performed to determine the exact change, and then ideally that SNP is studied in the lab to understand the consequence of the change on cellular function.

Sometimes mutations give super-human agility, strength, or intelligence. Other times they set us up to have wild and potentially unnecessary symptoms like Beast’s blue fur. Or perhaps equally annoying, the itchy watery eyes, nose, and throat from hay fever that come from a super-human response to harmless allergens.

A few notable candidate genes have been identified as associated with hay fever or with higher levels of circulating IgE antibodies, as we learned is a hallmark of atopy. Cytokines are the main signaling molecules that trigger activation of B cells to produce IgE antibodies, and not surprisingly, people with hay fever have mutations in genes that encode for cytokines or regulate their production. Also associated with hay fever are changes that enhance and stabilize the IgE receptor on mast cells and basophils, contributing to more intense symptoms. Genes responsible for airway smooth muscle contractions, contributing to cough and wheeze, are also implicated. SNPs have been identified in the genes encoding chemical mediators that cause ongoing symptoms such as leukotrienes, and in the specialized effector cells involved later in allergic inflammation response, such as eosinophils.

These are just a few examples of genes; dozens of others are being studied to learn exactly how they contribute to hay fever. Furthermore, some genes are only associated with allergies in the context of specific environments, further complicating the identification of true disease-causing genes. One clue that environmental factors influence allergies comes from studies of twins. Twin studies have shown that between monozygotic (identical) twins there is on average a 65% (range, 42-82%) chance that if one twin has allergies, the other will also have them. Between dizygotic (fraternal) twins, there is on average a 33% concordance rate (range 15-52%).

Some differences in twins are obvious, but other differences like allergies require epidemiological studies to tease apart.

The “hygiene hypothesis,” proposed by D. Strachan in 1989, became a popular basis to explore the increased incidence in allergic disease. Strachan observed that increased family size was associated with lower rate of allergies. He proposed that if allergies were prevented by early childhood infections, unhygienic contact with older siblings may protect against hay fever. Immune responses to pathogens like bacteria and viruses use a T-helper 1 (Th1) cell response. We know that Type I hypersensitivity reactions are mediated by Th2 cells’ stimulation of B cells to produce IgE antibodies. So the theory is that early childhood infections bias the immune system towards a Th1 response and suppress Th2 responses.

If Strachan’s hypothesis is correct, the Bates family should be allergen-free.

Strachan performed additional epidemiological studies to investigate the hypothesis that infections and larger family size protect against hay fever. He published a report in 2000 stating that decreases in family size do not appear to explain the increased incidence of allergies. Many additional studies looking into the protective effects of childhood infections have shown inconsistent results; some show a “protective” effect whereas others show either no association or early childhood infections correlated with development of allergies.

The “hygiene hypothesis” developed into a much broader “microflora hypothesis” which proposes that urbanization and a Western lifestyle limits our exposure to bacteria, viruses and parasites in general. Clean water, increased Cesarean sections, reduction in breastfeeding, increased antibiotic and antibacterial use, and reduced exposure to farm animals have limited our exposure to our microbial “old friends”. According to this idea, these “old friends” have evolved with us to the point where we require them for proper immune function.

 

“The Wonder Years” cast knew that we get by with a little help from our friends.

The diversity of our microbiome is decreasing, which may have detrimental effects on general health and the efficiency of our immune system. W. Parker proposed the term “biome depletion” to describe this current phenomenon. A few recommendations can be found here to increase microbial diversity in the gut.

Just like the Biodome, our biomes are not closed systems and can let in and respond to passer-byers, for better or for worse. In the case of Pauly Shore, it’s always for the worse.

If there weren’t already enough factors to consider in development of allergies, let’s peel back another layer. In addition to acquiring genes and microbiota from mothers during birthing and breastfeeding, in utero we are largely influenced by our mother’s environment through epigenetics. We’ve discussed epigenetics previously; briefly, it describes changes in the DNA and DNA-associated structural proteins that act to turn genes on or off. Epigenetic regulation either gives a green light or red light to production of specific gene products, or can act as a volume knob to finally tune gene expression. The process is plastic, allowing our genes to respond to the present environment.

Upon conception, epigenetic reprogramming occurs in the zygote, like a reset button. However, some epigenetic marks remain and are inherited by the offspring. So before and largely during pregnancy, the mother encounters various environments and the body responds using epigenetics to regulate genes at the appropriate time. These changes occur in the embryo or fetus as well, as a way to prime the baby for its eventual environment.

There is evidence that the immune system is under epigenetic regulation. At birth, atopy-prone infants tend to have diminished Th1 cell responses, thought to be influenced by the maternal environment. Additionally, maternal diet, microbial exposure, and smoking can influence epigenetic regulation of key genes involved in immune regulation and allergy development.

While there is no consensus on allergy prevention, there are many options for treatment of allergies, which will be discussed in the final allergy article in this series – coming soon!

Contributed by:  Julia van Rensburg, Ph.D.

Follow Julia on Twitter.

Dávila I, Mullol J, Ferrer M, Bartra J, del Cuvillo A, Montoro J, Jáuregui I, Sastre J, & Valero A (2009). Genetic aspects of allergic rhinitis. Journal of investigational allergology & clinical immunology, 19 Suppl 1, 25-31 PMID: 19476051

Grammatikos AP (2008). The genetic and environmental basis of atopic diseases. Annals of medicine, 40 (7), 482-95 PMID: 18608118

Strachan DP (2000). Family size, infection and atopy: the first decade of the "hygiene hypothesis". Thorax, 55 Suppl 1 PMID: 10943631

Parker W (2014). The "hygiene hypothesis" for allergic disease is a misnomer. BMJ (Clinical research ed.), 348 PMID: 25161287

Martino D, & Prescott S (2011). Epigenetics and prenatal influences on asthma and allergic airways disease. Chest, 139 (3), 640-7 PMID: 21362650