A recent article and accompanying commentary in the journal Pediatrics describe what we currently know about children who have died from influenza over the past decade or more. The Centers for Disease Control (CDC) has collected information about this since the 2003 – 2004 influenza season. In that first report there were 153 deaths. Since then there have been at least 100 influenza deaths annually among children. Several characteristics have not changed. About half of the deaths occur in children who were otherwise normal; that is, they had no underlying chronic condition that would predispose them to having more severe cases. Although the median age was 6 years, mortality was highest among the youngest children — those younger than 6 months. Most of the children who died, over 70%, had not been vaccinated against influenza. This is not a completely surprising finding since influenza vaccine is recommended for children 6 months or older. However, an important way to transmit the benefit of at least some immunity to infants and very young children is to vaccinate pregnant women since some protective antibody crosses over from mother to infant and lasts for several months at least. Currently only about a third of pregnant women are vaccinated.
Influenza is a stubborn and wily virus, traits that make designing a highly effective vaccine challenging. Its natural reservoir is several species of birds. It has 3 main subtypes, with the most serious disease typically coming from influenza A. The virus replicates itself in a way that results in frequent mutations, causing what is termed antigenic drift. This means the virus has the property of changing rapidly, making it something of a moving target for developing a vaccine against it. This is why our influenza vaccine changes every season in an effort to keep up with the rapid alterations. Immunity to last year’s version often doesn’t help much for this year. This also help explain why some years influenza is more mild, other years more deadly. There have been several severe pandemics from influenza when a particularly nasty version emerges, the most severe being in 1918-1919. That one killed over 50 million people.
These things make influenza vaccine one of our less effective vaccines. It reduces the incidence and severity of disease, but it cannot eliminate it outright, such as other vaccines directed against stable viruses like polio and smallpox can. Influenza is also notorious for paving the way for secondary infection from bacteria that happen to be resident in the respiratory system, such as staphylococci and streptococci. Many of the deaths are from such secondary infections. You can read much more about the details of the virus and its vaccine here and here.
In the USA the influenza season runs from fall until early spring. The graph above shows the past season’s trends in both documented and presumed cases (“influenza like illness”). The horizontal axis shows week of the year. The vaccine is based upon the best guess of experts who survey viral trends around the world. Some years they guess better than other years. It usually is available in October. The current vaccine is a killed one, meaning that, whatever you have read on the internet, you cannot get the infection from the vaccine. Two doses are recommended for children who have not previously received it (specifics here). Like all pediatric experts, I highly recommend it. Health care workers such as me are required to get it. I agree with the author of the commentary cited above that our best approach for reducing the death rate in children too young to get the vaccine themselves is increasing the vaccination rate in pregnant women.
Croup is an ancient illness — its very name comes from the Anglo-Saxon word to croak, which is what children with croup can sound like. The characteristic brassy cough sounds more like a seal to our modern ears, though. Also characteristic is a sound we call stridor, the sound of air rushing through a narrowed tube, in this case the child’s upper airway.
Croup is caused by viral infection of the region just below the vocal cords. One of several viruses can do it, but the usual offenders are members of the parainfluenza group. Although we have a vaccine for influenza, there is no vaccine to prevent parainfluenza; in spite of the similarities in their names, the two viruses are not related at all. The infection causes swelling, and the swelling causes narrowing of the airway. This makes it more difficult for the child to breath — in some ways it is like breathing through a straw — and the child has to work harder to get air in. This can make the child’s chest cave in the wrong way with each breath, something called retractions. Fever, if present, is usually mild. Here’s a neck x-ray of a child with croup. You can see with the arrow how narrow the airway, which on x-ray is a black air column, can be — often just a millimeter or so in diameter in more severe cases.
As with most viral illnesses, there is no specific treatment for croup. What treatment we have is directed at relieving the symptoms of throat pain and difficulty breathing. We do have several effective ways of doing this. Simple mist, as from a steamy bathroom, is a time-honored therapy to help a child breath and it helps with the throat pain. Croup generally occurs during the colder weather months. Another old remedy is to take the child out into the cold night air for a few minutes. I’m not sure why, but I think this actually helps, perhaps because cold shrinks the inflamed airway tissues. Inhaling a mist of the drug epinephrine definitely shrinks the swollen tissues, although it only lasts for an hour or two. The steroid drug dexamethasone, either orally or by injection, has become a standard therapy for moderately severe croup and it is quite effective because steroids reduce swelling. This therapy takes a couple of hours to work, though, because it needs to work its way into the tissues via the blood stream to exert its effects. More recently we’ve sometimes used inhaled steroids delivered as a mist, and that has been shown to improve the situation by directly delivering the steroid to the the affected area. Acetaminophen or ibuprofen can treat fever and throat pain.
When should you bring your child to the doctor for croup? A good rule of thumb is if your child has stridor when sitting quietly, termed stridor at rest, or if there are any retractions present — both of these are indications for an evaluation and possible therapy with epinephrine or dexamethasone. Another reason would be if your child refuses to drink enough. If your child has fever and drooling, refusing to swallow, as well as difficulty breathing that could be a much more serious infection called epiglottitis. That requires immediate attention in the emergency department.
We always see a few children in the PICU with severe croup, usually those who need repeated doses of epinephrine or are working very hard to breath. On very rare occasions we need to use a breathing tube and a mechanical ventilator for these children to bypass the obstruction until it clears on its own. Nearly all children, however, recover from croup with no complications.
Burnout has been a descriptive term for years, but lately psychologists and others have assigned it specific characteristics with a view toward being able actually to study and measure it. One common definition of burnout is a state of chronic stress that leads to physical and emotional exhaustion, cynicism, detachment, and feelings of ineffectiveness. The PICU environment is often one of high stress, so it’s a place where this can happen. We’ve known that informally for a long time. The best measure of this probably is that you don’t find many pediatric intensivists my age (66) who are still practicing; a large number go into something less stressful and with more regular hours. A recent study appearing in the principal journal in our field, Critical Care Medicine, attempted to measure more precisely how common burnout is among my colleagues. There have been many studies about burnout in physicians generally but none specific to pediatric critical care.
The authors used a voluntary online survey in which they identified by professional societies and other means 686 pediatric intensivists and asked them to answer a series of questions. Note this means the subjects were self-selected, decreasing the power of the findings. Also note how few pediatric intensivists there actually are in this country — we continue to have a shortage. The questions were in the form of an often used and validated tool for assessing burnout — the Maslach Burnout Inventory. 253 intensivists responded. Full disclosure: I didn’t respond, mainly because I just didn’t get around to it.
The subjects had ages between 41 and 60 years (I would have been a big outlier in this age spread), were 60% male, and 69% had been in practice for more than 10 years. The great majority were married and had children. The most common practice setting was an academic hospital or a community hospital affiliated with an academic center, which is in line with where you will find PICUs. The authors found that half the respondents scored high in at least one of the three burnout subscales. Emotional exhaustion, at 34%, was the highest, followed by low personal accomplishment at 21% and depersonalization at 20%. Burnout was twice as common among women physicians than among men. What the MBI defines as severe burnout was present in 21% of the respondents. That last figure is pretty high. For comparison, though, burnout rates among all physicians have been reported to be as high as 50%, with emergency medicine physicians reporting the highest rate. But you need to be careful here. I have no symptoms of burnout; I also didn’t do the survey. We need to beware of sampling error issues, with the most burned out physicians taking the time to do the survey. A recent survey of family practice physicians who had been in practice for 5 years or more illustrates this. In a survey of 2,099 physicians with a 100% capture rate, burnout was reported in 25%, half what other surveys with nonrandom samples have reported. The capture rate was so high because they rolled the survey into board recertification. That’s still a lot higher than we would like, of course; if I were in charge I’d aim for a practice environment that resulted in figures of 1-2% or so. So maybe pediatric intensivists are pretty much like everybody else.
Burnout does have consequences. A third of the respondents to the PICU survey reported symptoms of severe psychological distress during the previous month. Burnout has been linked to early retirement or changing practice fields. What do we know about preventing burnout? Interestinly, most of the literature on the subject points in particular not to the life and death decisions aspect of practice. A big thing is workload, something that should be obvious; work people to death and they will crack. Nearly as important as workload are the relentlessly annoying bureaucratic things physicians are increasingly required to do. These are things that take us away from the bedside, and recent time flow studies document that physicians are spending less and less face to face time with their patients and more time facing their computers. For a lot of the day we’re not doctors at all — we’re clerks. I can vouch that hardly a day goes by when I don’t open my institutional mail and find yet some new thing I’m supposed to do or check. Nothing, absolutely nothing, is ever reduced — things are continually piled on. It all adds to workload and to the feeling administrators don’t really understand or respect what practicing physicians actually do.
I’m not burned out myself. In fact, I’ve never felt burned out. I’m really not sure why this is. But I think it’s because I’ve managed to end up in work environments that are a good fit for me. I’m grateful to have lucked into that (and it was luck) because I continue to enjoy PICU practice. Studies like this, however, should remind us burnout continues to be huge and growing problem in our physician workforce. Many facilities are taking baby steps to address the problem by reducing the bureaucratic burden with nonphysician helpers. But the workload issue will be a pernicious problem. Specialties like pediatric critical care are already short of practitioners, so just adding more physicians is difficult. Besides, adding more physicians to a PICU practice increases costs without generating more revenue, and I doubt any institution will be enthusiastic about doing that. There are no workload standards to point to as benchmarks.
I’m not sure what will happen with the burnout issue. But I think we’re reaching some kind of critical threshold that will demand institutions address it with fundamental alterations in practice management, not just Bandaids that keep physicians from rising up in revolt but still keep the pot simmering. I’ll probably be retired by then, but maybe not.
Our human view of reality partly evolved through understanding things by observing subsequent events. Fifty thousand years ago imagine one proto-human saying to another, or however they communicated back then: “Don’t eat those berries – you’ll get sick afterwards.” Or an experienced proto-human might point to black clouds in the sky and predict severe weather was sure to follow. These things were learned and passed on through noting what tends to follow what. Such observational skills contributed to how we became the creatures we are, how we surpassed other species in development and achieved mastery of the word around us. But even many millennia ago I’m sure this habit of thinking created problems. What if it was a mere coincidence B followed A, and there was no causal link at all? If one is predisposed to view one thing as a consequence of another thing because it followed afterwards serious mischief is possible. A person violates a social taboo and disaster follows – cause and effect? Of course that’s true, if you see the world that way. In thirteenth century France, or for that matter in seventeenth century Massachusetts, an old woman nobody liked might pass by a neighbor’s house and glare at a milk cow blocking her way. Afterwards the cow goes dry. Arrest the witch!
This inherent way of looking at the world, often termed the fallacy of post hoc, ergo propter hoc (after that, therefore because of that) is deeply embedded in our human consciousness, in the way in which we explain events in the world around us. It often continues to serve us well today. Consider the old Vaudeville joke: “Doc, whenever I do this I hurt!” To which the physician responds: “Then stop doing it.” Common sense, right? Well, in the world of vaccine denial, this primeval human instinct can significantly cloud our thinking.
For those of you not familiar with this topic, there exists a substantial group of people who claim vaccines don’t work. More than that, they believe vaccines cause substantial harm. Why do they claim this? You could say their answer is partly theological: they already believe, a priori, vaccines are harmful, and once one believes that the only thing needed is to discover precisely how vaccines cause harm. I follow the vaccine denial world a bit online and it’s fascinating to watch them chase first this butterfly, then the next, pursuing the One True Cause of vaccine harm. They’re not looking to understand, really, they’re looking for evidence of what they already know to be true. Not surprisingly, some of the “proofs” they arrive at for vaccine harm contradict one another, providing another interesting parallel with medieval scholastic theology.
Vaccine denialists have a particular problem dealing with the science of epidemiology. You will read multiple online claims vaccines killed or injured a particular child because the child had problems after receiving a vaccine. In fact, it’s so obvious to them they are astonished anyone would question that, for example, a child who dies of sudden infant death syndrome (SIDS) and who received a vaccine several days previously was not killed by the vaccine. Post hoc, ergo propter hoc. Of course we use epidemiology to evaluate this issue. Just on the face of it, vaccines are given so frequently in the first 6 months of life that there is a large pool of infants who have been recently vaccinated. The pool is orders of magnitude larger than the incidence rate of SIDS (3 per 1,000). So a significant number of SIDS victims will have been recently vaccinated. The way epidemiology evaluates questions like this is to do case-control studies. Many of these have been done; all show show no adverse effects of the vaccine. Some actually show some protective effect of vaccination against SIDS.
Epidemiology is the study of diseases in populations. Over the past century it has become extremely sophisticated in how it answers questions such as the one at hand: “Do vaccines cause X (fill in whatever your particular claim of harm is for X)? Several standard epidemiological methods have been used to address this question, including case-control and cohort studies. Vaccine denialists, in my online experience, are simply either unwilling or incapable of dealing with the ramifications of this important field of medical research. To some extent I sympathize with them; understanding epidemiology is tough. They can be incredulous that I don’t accept that some event following a vaccination is obviously caused by it. Yet the key goal is to eliminate the “burn the witch” tendency humans have always had.
I’m actually not optimistic the core base of vaccine denialists is going to give up their theology any time soon. Many have invested enormous emotional energy into that world view, and change is very difficult. Many have children suffering from disorders for which we don’t have any good explanations, and “vaccine injury” provides a comforting way both to explain their child’s problems and to blame an outside agent for the problem. Of course the epidemiological evidence is that vaccines are extremely safe and effective. They are the most low risk and high benefit therapies modern medicine has to offer.
Traumatic brain injury (TBI) is unfortunately a fairly common thing seen in a typical PICU. Around a half million children are seen in America’s emergency departments each year for head injury. About half of these are mild, but 16-20% are classified as severe. Like most experienced pediatric intensivists, I have seen hundreds of these children over the years, with dozens at least in the severe category. In one sense the term “traumatic brain injury” has limited usefulness because it covers such a wide range of injuries, from mild concussions to more extensive injury, to lethal damage. There can be an associated skull fracture, but often there isn’t. In another sense, however, it’s a useful diagnostic category because the brain responds to a wide variety of injuries in a similar, stereotypic way. In fact several organs are like that, such as the lung.
Our understanding of the manifestations of TBI has grown considerably over the years I’ve practiced. When head CT scans became available we could for the first time assess such things as bleeding inside the skull or swelling of the brain easily and safely, things that allow us to direct our therapy appropriately. I remember how exciting it was when I was a medical student in 1974 doing neurology to see the first simple CT images taken on grainy Poloroid snapshots. Now CT can give us sophisticated, high resolution computer reconstructions of the brain. The technology represented such a breakthrough that its inventors received the Nobel Prize for it.
We soon realized, however, that some injuries to the brain, particularly what we call shear injury, are not well seen on CT — it takes an MRI scan to do that; the CT scan may actually look fairly normal. Another name for this is diffuse axonal injury, which is a good description of what happens. Shear injuries are caused by rapid acceleration/deceleration or rotation of the brain inside the skull from, for example, an impact at highway speeds. They can happen even without a physical blow to the head. These shearing forces essentially break some of the wiring that connects one part of the brain to another. Shear injury can be mild or it can be lethal — it just depends on the circumstances. That aspect is frustrating. Very similar injuries to two different patients can cause significantly different damage between them.
We also came to realize the most important thing we could do in the PICU for a child with severe TBI was to make sure the injury did not get worse: simple supportive measures like relieving pain and keeping the heart and lungs working well were key supportive measures to use while we waited for the child’s brain to heal. We learned to distinguish between what we term primary injury, the initial trauma, and secondary injury, which is what can happen in the succeeding hours to days as the brain responds to the primary injury. Early in my career we didn’t understand that distinction very well. We assumed there was little we could do except wait to see how severe the injury was. Now we understand everything we do during the critical period following the primary injury is crucial for outcome as we support the child during the healing phase. In particular, what first responders do in the field is crucial to what happens afterwards.
Increasing understanding of milder forms of TBI have made us realize it is much more common than we once thought. For children, although the long-term outcome for mild to moderate TBI is good, persistent problems with such things as headache, mood changes, and difficulties in school are not uncommon, and these can last for months. We also are coming to understand the bad effects of repeated injury, even if each individual event is mild. The effect can be cumulative. The disorder known as chronic traumatic encephalopathy was recognized, especially among professional football players who experience years of repeated blows to the head.
There is a great deal of information available about TBI. There are many misconceptions about it, too. As usual, Google can be a mixed blessing. You can find authoritative, respected advice from the Brain Trauma Foundation. This is an outstanding organization and you can also learn there some of the specifics of how we manage traumatic brain injury and why. This is also a useful site for more information.
It shouldn’t need to be said, but put a helmet on you child when they are skateboarding, skiing, or riding a bike. That’s enormously important to preventing or minimizing TBI.
We’ve known for some time the prevalence of obesity is growing among Americans — not just adults, but children, too. Obesity is associated with a long list of medical problems, including heart and other vascular diseases, diabetes, and joint problems. It is encouraging that recently the seemingly inexorable growth of pediatric obesity prevalence seems to have reached a plateau. But we still have a future problem looming for population health as these children grow up. A recent article in the New England Journal of Medicine evaluates a couple of key questions regarding obesity in children. The article, entitled “Simulation of Growth Trajectories of Childhood Obesity into Adulthood,” evaluates predictions of what will happen to our population health over the coming decades.
The authors used methods that are a bit complicated statistically and I’m certainly not competent to evaluate the details of them. But as I understand it they used existing data sets on childhood obesity to predict the prevalence of obesity at 35 years of age, the point at which the health risks of obesity begin to manifest themselves. Previous obesity studies had used fixed cohorts of individuals followed over time. The problem with that is that the dynamics of the population are changing, and presumably environmental risk factors as well. The model in this study allowed for new individuals to be constantly joining the cohort to control for these effects.
At any rate, the findings of this simulation were striking to me. Panel A below from the paper uses several models to indicate that by mid-century just over half of the population will be obese. Panel B follows a hypothetical cohort of 2-year-olds that essentially predicts the same thing. The authors defined obesity in the usual way: a body mass index (BMI) of greater than 30, with BMI defined as weight in kilograms divided by the square of height in meters.
The authors’ overall conclusions are kind of a glass half-empty/half-full kind of thing for pediatricians. Their simulations indicate that around half of adult obesity is attributable to childhood obesity, and the rate of childhood obesity has been improving recently. That’s good and gives me hope for the future. Children who are not obese have a lower risk at being so at age 35, whereas those who are already obese in childhood have an extremely high risk of being obese at age 35. So as pediatricians we can have a huge effect on the problem of obesity in the adult population. In the authors’ words:
Although a broad range of public health and clinical efforts appear to have stabilized early childhood obesity rates, in this study we estimated that among children between the ages of 2 and 19 years in 2016, more than half (57.3%) will be obese by the age of 35 years. . . . about half of the total prevalence of obesity began in childhood, and adult-onset obesity by 35 years of age accounted for the rest.
It’s a sobering thought that over half of adults will be obese. There are various theories to explain this, but I think the common sense one is best: we eat more calories and our lives are progressively more sedentary. The processed foods many of us eat are extremely dense in calories compared to meals we used to eat. Some evidence has implicated the increasing use of high-fructose corn syrup in such foods. These changes in diet and lifestyle have occurred very rapidly and we have not adapted. Pediatricians can help in the needed adaptation because all obese adults started out as children.
I majored in history of religion in college and have always had an interest in the places various twists and turns of theology can lead people. One relatively recent wrinkle is what has been loosely termed prosperity gospel or prosperity theology. It’s built upon the basic notion good things happen to good people and bad things happen to bad people. Of course that’s a foundational viewpoint of much of Christianity in the sense that virtue is rewarded and sinful behavior is punished in the great beyond. Protestant groups with strong traditions of predestination theology don’t see things exactly that way, but over the past century I think it’s fair to say most American denominations believe virtue is eventually rewarded (or is its own reward). The key word here is eventually.
Prosperity gospel, the origins of which most historians place in the 1950s or so but which really blossomed with the advent of televangelists, puts a new wrinkle on the centuries-old formulation of rewarding virtue. The basic idea is that faith and good works are not only rewarded in the next life, but also in this one. And that reward is very concrete. If your faith is strong you will be rewarded with success, especially riches in this world, as evidence of God’s favor. The darker, flip side to this viewpoint is that poverty is largely a person’s fault and perhaps even a sign of God’s disfavor. An extension of this way of thinking is the implicit, or sometimes explicit idea that personal good health and a happy, healthy family are also signs of godliness; in contrast, ill health or sickness in one’s family represent the reverse. It’s the second of these I’ve seen poison situations in the PICU.
Families with critically ill or injured children in the PICU are under enormous stress. I have always regarded religious faith as generally a good thing for families to have because it often helps hold them together in such stressful times. But over the years I have also seen the toxic effects of parents thinking their child is ill because their faith has not been strong enough. Parents often come to the PICU with this kind of thinking already bothering them in nonreligious ways: “I shouldn’t have driven down that road,” or “I shouldn’t have let my child go swimming.” If one adds to that: “My faith was not strong enough,” you can easily see where this can lead. The absolute worst cases I’ve seen are when families belong to a church group whose members imply a child’s misfortune is proof of the substandard zeal of the parents. It’s devastating.
Now and then I’ve spoken about this to pastors and ministers who participate to some degree in prosperity gospel thinking. Not surprisingly, all deny such a thing is a problem. But the more thoughtful ones understand how it can happen. To me it’s an example of how the practical working out on the ground of abstract theology affects daily reality. I’ve always felt my background and training in religion has helped me greatly in practicing pediatric critical care. I work in one of the most technical fields of medicine, yet paradoxically what I do is in some ways the furthest removed from technology.
Most experienced pediatric intensivists, myself included, have encountered situations in which we, the doctors, believe continuing to support a child is unethical because it is not saving the life but prolonging the dying; whereas the child’s parents believe the opposite—that it is unethical to withdraw life support because all life is sacred, no matter the circumstances. Sometimes these situations arise because poor communication causes families to distrust the doctors. But sometimes both sides understand each other clearly, but still disagree profoundly about the proper thing to do. What happens then?
Doctors often make the argument that we should not prolong suffering, and most people agree with that in my experience. Establishing if a patient is actually in pain can be difficult, and anyway we virtually always have the means to relieve pain in these situations. More telling to me is the argument that families cannot compel physicians to act unethically, and futile care is unethical. (You can read an excellent piece about the history of this concept here.) Yet even then, in theory, the physician can simply withdraw from the case, although from experience I can tell you it is difficult to find another physician to take on cases like this, and abandoning our patient without finding them another physician is clearly unethical (and illegal). All hospitals, particularly large ones with PICUs, have ethics committees in place to help in these situations. The goal is to bring in people experienced with examining such questions and who have no connection with the particular case. The committee examines all points of view — family, physicians, PICU staff — and gives a recommendation. That recommendation, however, is in most places only advisory, not compulsory. What happens if the family and the child’s physicians still disagree about what to do?
Dr. Robert Truog, a medical ethicist at Harvard, discussed such a case from a decade ago here. It is an excellent introduction to the topic. One wrinkle, however, is that in Texas the 1999 Advanced Directives Act allows a hospital to act against a family’s wishes and withdraw futile care if the hospital ethics committee rules against them. I don’t know of any other state that allows this. The hospital must give ten days notice and attempt to transfer the patient to another provider. The law has not been without controversy. Dr. Truog provides a careful analysis of this particular case, which was a child named Emilio Gonzales with Leigh’s disease, a progressive neurological disorder that typically leads to death by two years of age. He makes a valid argument that the child in question was not suffering unduly. He also argues that continuing to provide life support as the child’s mother wanted, although costly, should not be a consideration because the number of such cases across America is small and thus the contribution of their care to the total national healthcare costs is trivial. He also points out that hospital ethics committees are inevitably weighted toward physicians and other healthcare professionals who are far more likely than not to agree with the treating physicians in the PICU. In the end he decides the Texas statute is not a good thing and should not be generalized nationally.
Rather than jeopardize the respect we hold for diversity and minority viewpoints, I believe that in cases like that of Emilio Gonzales, we should seek to enhance our capacity to tolerate the choices of others, even when we believe they are wrong.
I have been involved in several cases like the one Dr. Truog describes. Thankfully, in all but one the family and the doctors were ultimately able to reach an understanding both sides accepted. In the one case in which we could not agree, nature ultimately decided things for us, as she often does. That is what also happened with Emilio Gonzales, who died before the conflicts were resolved. For myself, I agree with Dr. Truog. We should do our best to explain and understand, not once but continually, and ultimately agreements will be reached in virtually all cases.
Cases such as this are extremely rare, but they remind me that the pediatric intensive care unit is a place where, if we pay attention, we can learn a great deal both about life and about ourselves.
This one isn’t about critical care or childhood illness but nonetheless I found it fascinating. Humans evolved with the constant force of the earth’s gravity. This is relevant to several of our organs, but the brain’s anatomy makes it especially important. The brain floats in spinal fluid encased inside the closed box of the skull. Gravity would be expected to affect the details of that. Indeed, studies of people who spent prolonged periods of time in bed in a head down position indicate this abnormal situation causes changes in the brain. The authors of this study examined what prolonged exposure to near zero gravity in space did to the brain. They used MRI imaging to study two cohorts of astronauts: those who experienced short space flights and those who spend many months in the space station. MRI is very good for things such as estimating brain volume and in particular studying the fluid in and around the brain. As a background, it has been known previously astronauts may experience some swelling of their optic nerves, with resultant visual disturbances, as well as elevated pressure inside the skull. The question was if these changes related to duration of time spent in space.
The data showed some significant differences. Astronauts in prolonged flights were more likely to have optic nerve swelling. Long flight subjects also had significant increases in the fluid volume inside their brains, as measure by ventricular size. The mechanism for that may be some obstruction of fluid flow from the center of the brain to the outer surface. There were several other differences noted in the article as well. Below is an MRI image showing one such difference, crowding of one of the brain sulci. The sulci are the fissures between the folds of the brain surface that allow the total surface area of the cortical part of the brain to be much larger than it would be otherwise. The importance of this is well shown by the problems experienced by children with the congenital condition lissencephaly, in which the brain is more smooth so cortical volume is much less. These are T2-weighted MRI images, in which fluid is shown as bright white. The images show the fluid down in the sulci, between the folds in the brain surface.
Images A and B show one astronaut before (A) and after (B) prolonged flight. Images C and D show a short flight astronaut before and after exposure to space. The white signal is fluid. If you look at the sulcus indicated by the asterisk in A and B you can easily see how the area is kind of squished down after prolonged flight. That particular astronaut also had visual disturbance symptoms. There is no difference in the before and after images of the short flight astronaut.
Besides being interesting I think this is important because it reminds us our bodies have evolved under a specific set of conditions, such as 21% oxygen concentration and the earth’s gravity. We have long known gravity is important to bone physiology because our bones rely on weight bearing to stay healthy. Now it appears the brain, too, often undergoes changes when exposed to zero gravity, changes which are physiologically important. Any planning for future space travel, say to Mars, needs to consider this and how to counteract detrimental changes. It is still unknown if these brain changes in the long flight astronauts persist for a long time once they return to earth; that is currently under study.
It’s fall in the PICU and we just saw our first severe case of respiratory syncytial virus (RSV) of the season. RSV is by far the most common cause of bronchiolitis in infants. To scientists, RSV is a fascinating virus with several unique properties. One of these is its behavior in the population. When it’s present, RSV is everywhere. Then it suddenly vanishes. There are exceptions to everything in medicine — I have seen sporadic cases during the off-months — but generally RSV arrives with a bang in mid-winter and then leaves suddenly in the spring. It’s the only virus that consistently and reliably causes an epidemic every year, although it often alternates more severe with milder visitations. RSV epidemics often have some regional variability. For example, often one city will have a much more severe epidemic than do others in other regions of the country. RSV has a high attack rate — the term scientists use for the chances a susceptible person will get the infection if exposed to it. That, plus our generally poor defenses against it, explain the frequent epidemics. Every year a new crop of susceptible infants enters the population. By the age of two virtually all children have had RSV infection.
One aspect of RSV that interests medical scientists is how poor a job our immune systems do in fighting it off. Virtually all children are infected with RSV during the first few years of life. Not only that, all of us are reinfected multiple times during our lives. Attempts at devising a vaccine for RSV have thus far been unsuccessful. In fact, early versions of an experimental vaccine seemed to make the disease worse in some infants, raising the possibility some aspect of our immune response to the virus actually contributes to the symptoms. RSV is generally not a serious illness, causing cough and some wheezing, but for some children it can be life-threatening. Usually these children are very small infants, especially those born prematurely, and those with underlying problems with their lungs or hearts. For those infants we have a monthly shot (called Synagis) that helps reduce the severity of RSV when they get it, and may even prevent a few cases, but it is not an ideal treatment. Older and otherwise normal children, such as toddlers, can also get severe cases. We have no idea why that is, although it appears to me children with established asthma often get more severe disease.
So what is bronchiolitis? What does it look like? In medical terminology, adding the ending “itis” to a word means whatever comes before is inflamed. Thus tonsillitis is an inflammation of the tonsils and appendicitis means an inflamed appendix. So bronchiolitis is an inflammation of the bronchioles, the final part of the system of air-conducting tubes that connect the lungs with the outside world. Beyond the bronchioles are the aveoli, the grape-like clusters of air sacs where the business of the lungs — getting oxygen into our bodies and carbon dioxide out — takes place. Bronchiolitis is a disorder of blocked small airways. This prevents air from getting in and out normally, primarily out. The bronchiole tubes are blocked from swelling of the walls and from debris caused by the RSV infection — bits of broken airway cells and mucous plugs. This picture shows what it looks like.
For my entire 35 year career we have had no specific treatments for RSV bronchiolitis. Various things have been tried over the years but nothing seems to help. Care is supportive, meaning we use oxygen, frequent suctioning of mucous, IV fluids or nasogastric tube feedings if the infant cannot drink, and a mechanical ventilator for severe cases. We just have to support the child until the infection passes. But researchers have not given up on an RSV vaccine. There are several candidate vaccines in the research pipeline and the World Health Organization predicted in 2015 we will have one within a decade.
If we don’t have a vaccine to prevent RSV, what about a drug to treat it, to inactivate the virus? Several agents, such as ribavirin, have been tried in the past and rejected. We may be making progress on that front, however. A new drug (GS-5806) has been identified that inactivates RSV in the laboratory. It has also been tested in normal adults. They were given the test drug and then challenged with the RSV virus. The drug did not prevent disease but it did significantly reduce the symptoms and the total viral burden. There are now several clinical trials underway testing the drug in adults who are at high risk for severe RSV, those with compromised immune system. It seems to help. That’s all fine, but what we really need is information if it works in infants and small children, and as of yet there are no clinical trials to answer that question. One from Australia was apparently started but then withdrawn, reasons not stated.
So, to answer my question in the title: Where are we with RSV prevention and treatment? I agree with WHO that we will eventually get a vaccine, a drug, or both. But right now we’re still stuck where we were when I started doing this in 1978 — supportive care. It’s frustrating but RSV is a wily virus. Right now the best thing parents can do is try to postpone their infant getting it for the first time, especially if your child was born prematurely.