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Otitis Media: The Case for Human Evolution in its Pathogenesis
Renowned pediatric otolaryngologist Dr. Charles Bluestone discusses the impact of evolution on the increased incidence of otitis media in infants and children.
Upon completion of this activity, participants should be able to:
- Provide evidence that as a consequence of adaptation for bipedalism humans are born at nine months gestation whereas birth should be after 21 months which contributes to the pathogenesis of otitis media in the first year of life.
- Provide evidence that as a consequence of adaptation for speech as well as facial flattening in humans the pharynx and larynx anatomy changed compared with our immediate ancestors
- Provide support for the hypothesis that as a consequence of facial flattening and adaptation for speech in humans, as compared with our immediate ancestors, the palatal muscles related to Eustachian tube function changed and may be related to the relatively high incidence of otitis media in humans as compared with other species in nature.
- Bluestone CD. Born too soon: Impact on Pediatric Otolaryngology. Int J Pediatr Otorhinolaryngol 2005; 69(1):1-8.
- Bluestone CD. Impact of evolution on the Eustachian tube. Laryngoscope 2008; 118(3):522-527.
- Bluestone CD. Galapagos: Darwin, Evolution and E.N.T. Laryngoscope 2009; 119(10):1902-5.
- Bluestone CD, Swarts JD. Human evolutionary history: consequences for the pathogenesis of otitis media. Otolaryngol Head Neck Surg 2010; 143(6):739-44.
Dr. Bluestone has no relevant relationships with proprietary entities producing healthcare goods or services.
The University of Pittsburgh School of Medicine is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.
The University of Pittsburgh School of Medicine designates this enduring material for a maximum of 0.75 AMA PRA Category 1 CreditsTM. Each physician should only claim credit commensurate with the extent of their participation in the activity. Other health care professionals are awarded (0.075) continuing education units (CEU) which are equivalent to 0.75 contact hours.
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Release Date: 12/26/2012 | Last Modified On: 12/26/2012 | Expires: 12/26/2013
I’m Charles Bluestone, I’m a Professor at the University of Pittsburgh School of Medicine and have been invited by your Program Committee to give you a story that I’ve been working on for about the last 5 years that I hope will help you in your practice and to understand the pathogenesis, the causes of otitis media that’s related to human evolution. So the title of my talk today is Otitis Media: The Case for Human Evolution in its Pathogenesis.
So we’ve already written quite a bit on this subject and as a matter of fact I hope that your organizers will give you a copy of the four articles that have been published in the literature since 19 – since 2005 that will help you understand what is going on with my talk, because sometimes I talk very fast but I write very slowly, and you can read it as slow as you want to.
So one of the most important articles that relates to this discussion today was published in December of 2010 in the Otolaryngology Head and Neck Surgery, as you all know that’s the Academy of Otolaryngology Head and Neck Surgery’s official publication by my colleague Dr. Schwartz ,who is an anthropologist, and myself. Dr. Schwartz has been important in my understanding of the evolutionary and anthropologic issue related to human evolution related to otitis media. So we are going to move on and talk about what we’re up to.
First of all is my hypothesis that humans are the only species in nature with the high incidence of otitis media. Other animals do get ear infections but it’s primary in the canal, ear canal, external otitis; but unusual to get otitis media. Now why would that be? Well, first of all fish have no middle ear, so how are they going to get middle ear disease? But when we got up into the land as amphibians we needed to transfer sound from the air medium to liquid which was in the inner ear, and you need a middle ear for that. Now a middle ear if it gets fluid in it causes hearing loss, so therefore hearing is essential in the wild. Why is that? If you’ve ever been in East Africa or South Africa where there is animals that are like chimps, monkeys and so forth and they are also panthers and snakes. The panthers and snakes love protein and they love to eat monkeys and chimps, so if you had a hearing loss you would be eaten up by your predator. So even though we have no absolute proof that other animals have had no significant amount of ear disease because ear disease is associated with hearing loss. So if otitis media was common in animals, hearing would be poor, it would be unfavorable for survival, and would be selected out, and that’s just common senses.
So why do humans have this unique incidence of otitis media, what’s different about us that our predecessors, the human-like ancestors we had over the last millions of years and also the animals who are like the great apes, the apes and the ape, gorilla, orangutan serve. Well there are three consequences I’d like to discuss this afternoon with you of human adaptations. One adaptation is the bipedalsm, one is the speech and one is the facial flattening.
Now bipedalism, we are going to discuss that, I reported that information in the International Journal of Otolaryngology in 2005, you can bring it up on your, your computer or get it from your library, and speech. We are the only species that has speech, it’s unique to humans. And what is that speech consequence to evolution related to the eustachian tube and that’s in 2008 in Laryngoscope and facial flattening, we don’t have a long face like other of our predecessors in the great apes, they have a long snout, we’ve had facial flattening and we’ll look at that. And I presented that in a paper called Galapagos related to this issue of otitis media and their nose and their throat in Laryngoscope 2009. So you’ve got four articles you can look up to see what the – the details of what I’m going to tell you now.
Now what about bipedalism related to this otitis media? Well, first of all when we stood upright a couple of million years ago, the issue was not a big problem in terms of being birthed, but when we developed a big brain, which makes us unique in the animal kingdom, we became born too soon. Now what does that mean? Well, if you look at chimpanzees who have almost the same genetic code as we do, they are off about 2 or 3%, they have a – they are on their knuckles, and this is the pan is the chimp, and of course homo is humans, and we stand up now and we have bipedalism. Now bipedalism is habitual bipedalism, some of the animals actually stand up a short time looking over the savannah to see if there is any predators, but they are not habitually bipedal. They are on – they are quadrupeds. So the habitual bipedalism resulted in a small pelvic outlet and together with our unique big brain we are born 12 months too early. We should be born at 21 months, not 9 months and that’s a known anthropologic and obstetric issue.
So if you look at the Pan, which is the chimp and the AL288-1, that’s Lucy, which was a predecessor of homo-sapiens, and then look at homo and the color brown is the size of the skull. Now if you look at the inlet midplane and outlet of the pelvis in Pan, that’s a chimp, and even in Lucy, who was one of our predecessors, the brain has a large space to get through that outlet, but look what happened in our humans. The human female pelvis is to small at the outlet, that’s over here to the right lower, you see that the brain has a tough time getting out, so what happens is we are the only species that needs help during birthing because you have to turn the head to get it out. So it’s hard for us to get our head out during birth and we are born 12 months too early.
So here is cartoon showing the chimp, the blue rectangle is the size of the pelvis in a cartoon and the chimp and then the gorilla, you see the – even the gorilla has – even though it has sort of a big head, gets through the pelvic outlet easily but in the human it’s even trouble getting out unless you turn it around and get it out that way, and as you know many children have to have Cesarian section to get out, etc. But we are the only species that over the span of homo-sapiens being born you need to have help getting out of the uterus, the vagina and uterus. So this is known to anthropologists. Martin, Professor Martin is a known superstar in anthropology and his book published 20 years ago, that humans really have a 21 month gestation, 9 months in utero and 12 months outside of utero.
So what is the problem with otitis media related to the first year of life when we should be born 12 months later? Well during the first year of life we have an immature eustachian tube, which is too short that structure and function that’s too floppy, the cartilage support of the eustachian tube is very floppy. We’ve shown that in temporal bone specimens and in function tests. Also, not related to the eustachian tube, but the immune system is very immature in the first year of life, as you know, and doesn’t really get more mature until about 1 year of age, better maturity by 6, and fully matured by 10 years of age. So prematurity is also a risk factor for otitis media. So if you are born with 9 months, that’s one risk factor, but if you are born at 7 or 8 months, that’s even worse, which I call born way too soon because it’s before 9 months even. So those kids are at risk for having otitis media because they are not really 9 months when they are born, they are 9 months minus something.
Also the impact of nurture, our predecessors who were homo-sapiens in the cave days, mothers would breast feed, we never heard of such things as milk, bottle – bottle feeding, and we know that breast feeding is good for prevention of ear disease and bottle feeding is lousy with cow’s milk. And the environment, they didn’t have day care centers, and they rarely smoked early on in our span of life for homo-sapiens and that causes increasing exposure to viruses and bacteria in day care and smoking causes probably – problems with cilia in the nose and eustachian tube. So why then would the ear disease most common when it presents itself in the first year of life, those are three good reasons why.
So what else other than our bipedalism, walking on two feet, and big brain is unique to humans? Let me just back up a little bit on why we think, or anthropologists think that bipedalism is better than quadrupeds. One is that by standing up you are looking out over the – over the savannah to look out for predators, whereas the quadruped may be able to get up like a gorilla, off the knuckles and look up over but we do it habitually. But the most important issue as most investigators think is that it allows us to use our hands, which have become very sophisticated, that’s our forepaws when you were a monkey or a chimp, and to make tools and to be able to defend yourself with weapons and also to get food with throwing arrows and swords, etc. So bipedalism is important in our development. So what else besides bipedalism and big brain is unique to humans?
Speech, as I said before speech is a unique characteristic of our species and no other species. So why is speech maybe related to otitis media? Well our vocal cord tract is longer and narrower and it’s called the unique two tube form and during that growth to give us better speech and vocalization it reduced palatable growth, the palate got shorter than in the nonhuman primate. That’s been shown. The descent of the larynx which happens after about 3 months of age in humans drops down to a level that’s much lower than any other animal, and that lengthens the laryngopharynx compared with the nonhuman primate in infants after the neonatal period, which is around 3 months.
As a matter of fact, obstructive sleep apnea, which most otolaryngologists, pediatricians, general practitioners and the late public know, is a big problem in obstructive sleep apnea that can cause – go on even to heart failure. That only occurs in humans in nature. There is one animal, the English bull dog which has an extremely large head and a very small throat, which has been bred that way because he’s – the English bull dog has a flattened face, which we’ll discuss in a few minutes about flattened face, and they get obstructive sleep apnea and they sometimes have to have surgery for that, like we do for adults with humans. Now also the head is so large that my veterinary friends tell me that when you have an English bull dog their head is so big it will not come through the vaginal tract without a C-section. So that’s not an animal that’s in the wild, that’s been bred and bred frankly I think in a poor way to cause trouble with an animal just to get a flat head and big head. It doesn’t make sense to me.
So if you look at this picture of the comparison of a chimp, the red being the palate and the bluish green is the epiglottis, and the chimp is on the left and the human is on the right you see that the adult who is on the right, a human, has a gap between the epiglottis, the green areas and the soft palate, which is the red, and compared to the chimp and the human baby before 3 months of age, well there’s a so-called lockup between the epiglottis and the palate. And that allows the animals before us, and the animals currently and babies up until 3 months to be able to such, breath, swallow without choking. But after 3 months of age our larynx drops as on the right side as you can see the human, the larynx drops to a level, almost to the level of the hyoid and therefore we are probably the only species that has choking and aspiration because of that issue. So we’ve had a consequence, the consequence is for obstructive sleep apnea and a consequence with – related to this issue of speech and also aspiration and even death if you aspirate into your lungs.
So how else are we different our ancestors? What other problems do we have that we have adapted to? Well we have lost our prognathism, or we’ve gotten facial flattening. As we showed you in that last picture, if you look at the last picture look at the snout on the left hand side of the chimp and look how flat our face is compared to the chimp. So we’ve lost our facial flattening from our ancestors who are the hominids that preceded homo-erectus and homo-sapien, and also the great apes, as I’ve just told you about. So why is that a problem?
Well, the problem is if you look at the homo-sapien, which is these pictures are forum, the top two are one is a lateral on the left and the one on top on the right, and on the left below is a frontal, and then the – underneath the surface of the skull, but you can see the maxilla and the fact is rather flattened as compared to the chimp. Look at the chimp’s huge prognathic jaw, that’s the upper jaw, huge difference between the chimp’s prognathic jaw and our face, which is flat. And here is the orangutan, even worse, look how prolonged that jaw is, look at all the teeth in the orangutan on the right lower. The teeth and look at all the molars including the third molar. That’s because we - _____ molar stuck up on our jaw, our wisdom teeth. So here is the gorilla, look at the size of that jaw compared to my first pictures of the human.
So why did we lose our prognathic jaw? It’s a hypothesis by a Harvard Professor Rangman who says that about 1.8 million years ago that story, our predecessors, the homo-sapien was homo-erectus, changed the diet. And how do we know that? Because in fossil recovery in parts of the world they can see where the – they have been cooking the food, the bones have been cooked of animals that they looked at in the same area that they found homo-sapiens in, home-erectus. So we’ve gotten our diet changed. What’s so important about cooking food? Well, it’s been said that gorilla’s spend almost 6 hours a day trying to chew food to get enough protein to support their need for calories, however we have by cooking it you can get more food into you and you have enough calories to provide your big brain that got so big during the homo-sapien from the homo-erectus.
So I also went to Galapagos in East Africa over the years and wanted to see what Darwin did about finches and how it relates to humans. And what’s that got to do with this whole discussion about this business of facial flattening? Well, Darwin noted after he got back that there are 13 specific species that are different from each other of finches. And it’s related to the islands that they are on and that eating is related to their niche, their eating niche on that island. Some eat seeds of – ground seeds, some eat from the cactus and the finch beak can be made similar, homologous to the maxilla and mandible. So the point is that the face changed in these animals and what was it caused by? A difference in the kind of eating that they did because they needed a special beak. Now if you think about the beak, isn’t the beak the maxilla and the mandible homology to our humans?
So here is the species that the finch which Darwin described in his famous book, The Origin of Species, and the Galapagos marine iguana he also noted, and that’s a unique species because the iguana in Latin America and South America is a land animal, but the iguana in the Galapagos has learned, adapted to eating algae off the lava rocks under the water and by doing that it got a short blunt nose. So there is an adaptation for scraping algae or food from the lava rocks under the ocean. So you can change the shape of your face and your eating habits, change the shape of your teeth and your jaw. And here is the marine iguana with a short flat face which is different than the land iguana which is so common in Latin America on the land and _______.
So what is this business about cooking? Well, in Rangman’s famous from 2009 he stated that cooking made homo-erectus 1.3 million years ago unique, and the ______ is that we lose our snout with our – when our mouth became smaller because we didn’t have to have all those teeth and the teeth changed due to changes in diet from cooking, as I related to you the third molar in those _______ of the great apes had the third molar exposed, our third molars are stuck up in the jaw, the wisdom teeth which you sometimes have removed, often removed when you are a late teenager. So our jaws became smaller, our mouth became smaller and our teeth were not needed to chew up food so aggressively and the canines, you don’t need all that when you cook the food. So cooking has changed the shape of the jaw.
So what other information do we have that might help us understand this problem? We have one animal model which we think is a in vivo model of otitis media and related to change in the shape of the skull. Well, it – this animal model has been bred over 300 years to have a short snout and it has chronic otitis media with effusion which the veterinarians know and call a primary secretory otitis media. Now lots of dogs have external otitis, that’s in the canal, but there are not very many dogs that have primary otitis media, and they do have it picked up on examination by otoscope or by MRI it’s almost invariably the short noted, flat nosed bred animals like the Beagles as a Beagle, the English Bull Dog, the Pekinese, all the ones with short faces, and especially the Cavalier King Charles.
The Cavalier King Charles looks like the one on the left here with that short face, and the other mixed breed is on the right. You see how a long snout and they don’t have ear disease anywhere near the incidence of 50% which the Cavalier has, so the shortened front to back diameter of the skull due to premature fusion of the coronal suture is related to this issue, and the pharynx became narrower, the tongue pushed back and as I told you before the English Bull Dog is the only animal that’s been bred to get snoring and also obstructive sleep apnea.
So the Cavalier King Charles Spaniel develops chronic, as the veterinarians call them, purulent, persistent rather, they call it persistent secretory otitis media, bred for its short nose. Now that’s called artificial selection, so if you know or have read the origin of the species Darwin got his idea about natural selection from artificial selection in botany and also in pigeons. But this is natural selection, with our loss of our prognathism. So these are Darwin’s terms from the origin of species, so natural selection, how humans lost their snout, artificial selection is how you do it by breeding those with short snouts with other snort snouters and then you get shorter and shorter, and it’s done by artificial breeding, like they do flowers.
So how did the Cavalier King Charles develop chronic persistent secretory otitis media? Their short snout changed the palatal anatomy. So the question is does the middle ear effusion with this very thick mucus in that Cavalier, it causes trouble by the way with hearing loss, have a consequence? There are two muscles that are related to this issue, the muscles that come from the palate, the tensor veli palatini, TVP, and the LVP muscles are altered causing the eustachian tube dysfunction, that’s our hypothesis. It’s a current research project which we are undergoing now.
So why would change in palate morphology secondary to facial flattening in humans be involved in the pathogenesis of otitis media? Now that facial flattening plus the shortening of the palate due to the change in the pharynx related to speech acquisition is a problem. So eustachian tube has these two muscles. Now if you look at this picture of a cross section of a human adult eustachian tube, if you look at the lettering on the right you see TVP, that’s the tensor and you see the tensor veli palatini is attached to the lateral edge of the cartilage, it’s a crook shank cartilage and the C stands for cartilage, and the L is for lumen, and the levator, which is the other muscle that is involved with the eustachian tube is that big round muscle called LVP. Look at the size of that muscle below there, huge.
So what about monkey’s eustachian tube anatomy? We’ve checked – we’ve had monkeys in our laboratory since 1978, they share 93% of our genetic code and their eustachian tube anatomy and function is similar to us and that’s why we used them for NIH studies at Children’s Hospital for the last 30, 40 years. But the function is similar but not identical, it’s not the same as ours.
The insertion of the tensor veli palatini in the eustachian tube cartilage in the monkey is much longer than our insertion. The humans have a shorter insertion in the tensor, so therefore the tensor is anatomically different than the monkey. The levator has a round belly and buts the inferior portion of the eustachian tube in humans but not in the monkey. And if you look at this comparison, these are from specimens that was dissected and analyzed by my colleagues Dr. Doyle, an anthropologist that was with us for 30 years, and Dr. Rood, the late Dr. Rood who was an anatomist. If you look at the human on the left you see the marking for LVP on the human is huge and the tensor is a slight slip where it says TVP. If you look at the Rhesus Monkey on your right side of your screen you’ll see that the tensor veli palatini is huge and the LVP is small. So these are different. Now if you look at the ratio of insertion on the Cartilages to the TVP muscle, that’s TVPM on this slide, and that’s related to the length of the cartilage, you see that you can put on down a ratio. So we have about 1/3 cartilage of muscle insertion on our cartilage as compared with the monkey. And by the way, in cleft palates even shorter than that, it’s shorter than humans without cleft palate, so that TVP is important in its anatomic differences with our primate friends, the monkeys.
So the monkeys have perfect eustachian tube function in contrast to we humans who have lousy physiologic function. We have difficulty opening our eustachian tubes, even though they are normal during function tests, we have problems in flying and scuba diving because we have lousy function. The monkey when we tested with negative pressure like coming down in an airplane or coming down in a scuba tank, scuba test, they have no problem in opening their eustachian tube no matter how much negative pressure you put on. They have perfect function, we have crummy function. So the conclusion is that a monkey has more efficient TVP physiologic opening mechanism than humans.
So what about the pathophysiology of the eustachian tube in humans? In humans with chronic otitis media effusion, which is quite common, and it’s the most common dysfunction related to chronic media effusion, that has been associated with constriction of the eustachian tube when they swallow, and we think it’s due to the levator because the levator is up under our eustachian tube as compared to the monkey, and it also is a huge bundle, a massive muscle there and it constricts instead of dilates the eustachian tube, which is the responsibility of the tensor muscle. So during swallowing there is a – there is a paradoxical constriction in patients that have chronic fluid in their ear, which is so common in adults and tough palate kids, which we find constriction.
So what’s the conclusion? Human evolution has a role in otitis media. It is hereditable, we know that, in fact Dr. Castlebrand who is in your audience today performed studies every month, she went to the clinic to see children who were twins, triplets and who twins who were homozygous and heterozygous and reported some 1999 I believe that there is heritability of otitis media and that’s probably high in females and still high but a little lower in males. And it’s also related to certain racial groups as you know the Aborigine of Australia, the Southwestern American Indian, Native Americans, the Navajos and the Apache have ear disease almost 100% by the time they are 1 year of age, as are Inuits, that is Eskimos of North America, and Alaska especially and Canada and there are also other, other racial groups that are more prone to ear disease and that may be related to craniofacial anatomy and eustachian palatal muscles.
What about nature? Well, it’s still the leading, the levator palatini constriction may be due to the impact of evolution as we showed you. So the unrepaired cleft palate infants is an in vivo model of chronic media effusion, very similar to the artificial selection of the Cavalier King Charles and they have chronic media effusion like the chronic cleft palate unrepaired clefts have chronic fluid just like the Cavalier have. So this is called a functional obstruction. Not anatomic, we don’t see any blockage of the tube but only when they swallow it doesn’t open, it’s reversed.
So what about the TVP? Well, short insertion of the eustachian tube, and that’s probably impacted evolution and the human physiology of the eustachian tube is poor, and that relates to recurrent acute otitis media, you can imagine it’s putting a patient in who is 1 or 2 years of age, let’s say 1 year of age, within the first year of life, 12 months, you put them in a day care, they get viral infection, they have lousy TV function, TVP function to begin with, they try to open their tubes when their tube is swollen with virus and how do you get it open? You get negative pressure, negative pressure leads to middle ear effusion or it sucks up bacteria from the back of the nose. I’m trying to make a very complicated problem quite simple, but I believe that’s the problem.
So what about nurture? Well lack of breast feeding as we’ve talked about, the exposure in day care to pathogens, smoking in the household has been shown to cut down mucociliary transport and use of pacifiers which as far as I’m concerned are related to sucking on the pacifier when your nose is open is not a problem, but sucking on a pacifier when your nose is closed, you get a lot of negative pressure in the back of your throat and that can shut down the eustachian tube and when it finally opens up it sucks junk from the back of your nose into your ear.
So what’s the conclusion? Otitis media is a human condition related to the consequences of evolution that is adaptations of bipedalism and the big brain, speech and loss of prognathism which is probably related to cooking, genetic issues, immunologic and environmental factors. So we’ve come a long way from being on all fours and our knuckles on the left hand side with the gorilla, and the descent to man has led us to be bipedal with a big brain and running the world we’ve gotten otitis media and some other diseases and disorders with our bipedalism. By bad back which is hurting me right now is related to me standing up on two feet, because on all four I probably wouldn’t have a bad back. Thank you very much.