The Body, page 24
*1 The bursa of Fabricius is named for Hieronymus Fabricius (1537–1619), an Italian anatomist who thought it was connected to the production of eggs. Fabricius was wrong, but its actual purpose remained a mystery until 1955, when it was solved by a happy accident. Bruce Glick, then a graduate student at Ohio State University, removed bursas from chickens to see what effect it had on them in the hope of solving the mystery. But the removals had no discernible effect, so he gave up on the problem. The chickens were then passed on to another student, Tony Chang, who was studying antibodies. Chang discovered that the birds without bursas produced no antibodies. The two young researchers realized that the bursa of Fabricius was responsible for antibody production—a really big discovery in immunology. They submitted a paper to the journal Science, but it was returned as “uninteresting.” Eventually, they got it published in Poultry Science. It has since become “one of the most cited papers in immunology,” according to the British Society for Immunology. “Bursa,” incidentally, comes from a Latin term for “bag” or “purse” and can describe various structures. Bursas in humans (which are responsible for bursitis) are little sacs that help to cushion joints.
*2 Crohn didn’t use the term himself, preferring instead to call it regional ileitis, regional enteritis, or cicatrizing enterocolitis. It was later discovered that Thomas Kennedy Dalziel, a Glasgow surgeon, had described the same disease almost twenty years earlier. He called it chronic interstitial enteritis. Crohn obituary, New York Times, July 30, 1983; “Crohn of Crohn’s Disease,” Gastroenterology, May 1999.
13 DEEP BREATH: THE LUNGS AND BREATHING
I am in the habit of going to sea whenever I begin to grow hazy about the eyes, and begin to be over conscious of my lungs.
—HERMAN MELVILLE, MOBY-DICK
I
QUIETLY AND RHYTHMICALLY, awake or asleep, generally without thought, every day you breathe in and out about 20,000 times, diligently processing some 4,000 gallons (or 440 cubic feet) of air, depending on how big you are and how active. That’s about 7.3 million breaths between birthdays, 550 million or so over the course of a lifetime.
In breathing, as in everything in life, the numbers are staggering—indeed fantastical. Every time you breathe, you exhale some 25 sextillion (that’s 2.5 x 1022) molecules of oxygen—so many that with a day’s breathing you will in all likelihood inhale at least one molecule from the breaths of every person who has ever lived. And every person who lives from now until the sun burns out will from time to time breathe in a bit of you. At the atomic level, we are in a sense eternal.
For most of us, those molecules come pouring in through the nares, which is what anatomists call the nostrils (for no very compelling reason, it must be said). From there the air passes through the most mysterious space in your head, the sinus cavity. Proportionate to the rest of the head, the sinuses take up an enormous amount of space, and no one is at all sure why.
“Sinuses are strange,” Ben Ollivere of the University of Nottingham and Queen’s Medical Centre told me one day. “They are just cavernous spaces in your head. You would have room for a good deal more gray matter if you didn’t have to devote so much of your head to the sinuses.” The space isn’t a complete void, but rather is riddled with a complex network of bones, which are thought to help with breathing efficiency, though no one can say quite how. Whether or not they have a function, the sinuses cause a lot of unhappiness. Thirty-five million Americans suffer sinusitis every year, and about 20 percent of all antibiotic prescriptions are for people with sinus conditions (even though sinus conditions are overwhelmingly viral and thus immune to antibiotics).
Incidentally, the reason your nose runs in chilly weather is the same reason your bathroom windows run with water in chilly weather. In the case of your nose, warm air from your lungs meets cold air coming into the nostrils and condenses, resulting in a drip.
The lungs are also wonderfully good at cleaning. According to one estimate, the average urban dweller inhales some twenty billion foreign particles every day—dust, industrial pollutants, pollen, fungal spores, whatever is adrift on the day’s air. A lot of this stuff can make you very ill, but it doesn’t, by and large, because your body is normally adept at challenging intruders. If an invading particle is big or especially irritating, you will almost certainly cough or sneeze it straight back out again (often in the process making it someone else’s problem). If it is too small to provoke such a vehement response, it will in all likelihood be trapped in the mucus that lines your nasal passages or caught by the bronchi, or tubules, in your lungs. These tiny airways are lined with millions and millions of hairlike cilia that act like paddles (but beating furiously at sixteen times a second), and they swat the invaders back into the throat, where they are diverted to the stomach and dissolved by hydrochloric acid. If any invaders manage to get past these waving hordes, they will encounter little devouring machines called alveolar macrophages, which gobble them up. Despite all this, occasionally some pathogens get through and make you sick. That’s the way life is, of course.
Only recently has it been discovered that sneezes are a much more drenching experience than anyone thought. A team led by Professor Lydia Bourouiba of MIT, as reported by Nature, studied sneezes more closely than anyone had ever chosen to before and found that sneeze droplets can travel up to eight meters and drift in suspension in the air for ten minutes before gently settling onto nearby surfaces. Through ultra-slow-motion filming, they also discovered that a sneeze isn’t a bolus of droplets, as had always been thought, but more like a sheet—a kind of liquid Saran Wrap—that breaks over nearby surfaces, providing further evidence, if any were needed, that you don’t want to be too close to a sneezing person. An interesting theory is that weather and temperature may influence how the droplets in a sneeze coalesce, which could explain why flu and colds are more common in cold weather, but that still doesn’t explain why infectious droplets are more infectious to us when we pick them up by touch rather than when we breathe (or kiss) them in. The formal name for the act of sneezing, by the way, is sternutation, though some authorities in their lighter moments refer to a sneeze as an autosomal dominant compelling helio-ophthalmic outburst, which makes the acronym ACHOO (sort of).
Altogether the lungs weigh about 2.4 pounds, and they take up more space in your chest than you probably realize. They jut up as high as your neck and bottom out at about the breastbone. We tend to think of them as inflating and deflating independently, like bellows, but in fact they are greatly assisted by one of the least appreciated muscles in the body: the diaphragm. The diaphragm is a mammalian invention and it is a good one. By pulling down on the lungs from below, it helps them to work more powerfully. The increased respiratory efficiency that the diaphragm brings enables us to get more oxygen to our muscles, which helped us to become strong, and to our brains, which helped us to become smart. Efficiency is also assisted by a slight differential in air pressure between the outside world and the space around your lungs, known as the pleural cavity. Air pressure in the chest is less than atmospheric pressure, which helps to keep the lungs inflated. If air gets into the chest, because of a puncture wound, say, the differential vanishes and the lungs collapse to only about a third of their normal size.
Breathing is one of the few autonomic functions that you can control intentionally, though only up to a point. You can shut your eyes for as long as you wish, but you cannot shut off your breathing for long before the autonomic system reasserts itself and compels you to breathe. Interestingly, the discomfort you feel when you hold your breath for too long is caused not by the depletion of oxygen but by a buildup of carbon dioxide. That’s why the first thing you do when you stop holding your breath is blow out. You would think that the most urgent need would be to get fresh air in rather than stale air out, but no. The body so abhors CO2 that you must expel it before gulping in replenishment.
Humans are pretty poor at holding their breath—indeed, are inefficient breathers altogether. Our lungs can hold about six quarts of air, but normally we breathe in only about half a quart at a time, so there is plenty of scope for improvement. The very longest any human being has voluntarily held his breath was twenty-four minutes and three seconds by Aleix Segura Vendrell of Spain, who did it in a pool in Barcelona in February 2016, but that was after breathing pure oxygen for some time beforehand and then lying motionless in the water to reduce energy demand to a minimum. Compared with most aquatic mammals, this is really poor. Some seals can stay underwater for two hours. Most of us can’t last much more than a minute, if that. Even the famous lady pearl divers of Japan, known as the ama, don’t stay underwater for more than about two minutes normally (though they do make a hundred or more dives a day).
All in all, it takes a lot of lung to keep you going. If you are an averagely sized adult, you will have roughly twenty square feet of skin, but about a thousand square feet of lung tissue containing about fifteen hundred miles of airways. Packing such a lot of breathing apparatus into the modest space of your chest is a nifty solution to the very considerable problem of how to get a lot of oxygen efficiently to billions of cells. Without that intricate packaging, we might have to be like kelp—hundreds of feet long but with all the cells very near the surface to facilitate oxygen exchange.
Considering how complex an operation respiration is, it is not surprising that the lungs can cause us a lot of problems. What is perhaps surprising is how little we sometimes understand the causes of these problems, and of no condition is that more true than asthma.
II
IF YOU HAD to nominate someone to be a poster figure for asthma, you could do worse than the great French novelist Marcel Proust (1871–1922). But then you could nominate Proust as a poster figure for a great many medical conditions because he had a superabundance of them. He suffered from insomnia, indigestion, backaches, headaches, fatigue, dizziness, and crushing ennui. More than anything else, however, he was a slave to asthma. He had his first attack at nine and passed a wretched life thereafter. With his suffering came an acute germ phobia. Before opening his mail, he would have his assistant place it in a sealed box and expose it to formaldehyde vapors for two hours. Wherever he was in the world, he sent his mother detailed daily reports on his sleep, lung function, mental composure, and bowel movements. He was, as you will gather, somewhat preoccupied with his health.
Though some of his concerns were perhaps a touch hypochondriacal, the asthma was real enough. Desperate to find a cure, he submitted to countless (and pointless) enemas; took infusions of morphine, opium, caffeine, amyl, trional, valerian, and atropine; smoked medicated cigarettes; inhaled drafts of creosote and chloroform; underwent more than a hundred painful nasal cauterizations; adopted a milk diet; had the gas to his house cut off; and lived as much of his life as he could in the fresh air of spa towns and mountain resorts. Nothing worked. He died of pneumonia, his lungs worn out, in the autumn of 1922 aged just fifty-one.
In Proust’s day, asthma was a rare disease and not well understood. Today it is common and still not understood. The second half of the twentieth century saw a rapid increase in asthma rates in most Western nations, and no one knows why. An estimated 300 million people in the world have asthma today, about 5 percent of adults and about 15 percent of children in those countries where it is measured carefully, though the proportions vary markedly from region to region and country to country, even from city to city. In China, the city of Guangzhou is highly polluted, while nearby Hong Kong, just an hour away by train, is comparatively clean as it has little industry and lots of fresh air because it is by the sea. Yet in clean Hong Kong asthma rates are 15 percent, while in heavily polluted Guangzhou they are just 3 percent, exactly the opposite of what one would expect. No one can account for any of this.
Globally, asthma is more common among boys than girls before puberty, but more common in girls than boys after puberty. It is more common in blacks than whites (generally but not everywhere) and in city people than rural people. In children, it is closely associated with both being obese and being underweight; obese children get it more often, but underweight children get it worse. The highest rate in the world is in the U.K., where 30 percent of children have shown asthma symptoms. The lowest rates are in China, Greece, Georgia, Romania, and Russia, with just 3 percent. All the English-speaking nations of the world have high rates, as do those of Latin America.
There is no cure, though in 75 percent of young people asthma resolves itself by the time they reach early adulthood. No one knows how or why that happens either, or why it doesn’t happen for the unfortunate minority. Indeed, where asthma is concerned, no one knows much of anything.
Asthma (the word comes from a Greek term meaning “to gasp”) has become not only more prevalent but more commonly lethal, and often quite suddenly. Among children who died between 1959 and 1966 in Great Britain, the proportion whose deaths were attributed to asthma leaped from 1 percent to 7.2 percent, and there were similar increases in Ireland, Norway, Australia, and New Zealand. These were linked to side effects of asthma medications that were heavily used in those countries at that time, and the death rate fell when the use of those medications was reduced. However, asthma remains the fourth leading cause of childhood death in Britain. In the United States, between 1980 and 2000 asthma rates doubled, but hospitalization rates tripled, suggesting that asthma is now not only more common but more severe. Similar rises have been found throughout much of the developed world—in Scandinavia, Australia, New Zealand, some of the richer parts of Asia—but not, curiously, everywhere. Japan, for instance, has not seen a great increase in asthma rates.
“You probably think asthma is caused by dust mites or cats or chemicals or cigarette smoke or air pollution,” says Neil Pearce, professor of epidemiology and biostatistics at the London School of Hygiene and Tropical Medicine. “I have spent thirty years studying asthma, and the main thing I have achieved is to show that almost none of the things people think cause asthma actually do. They can provoke attacks if you have asthma already, but they don’t cause it. We have very little idea what the primary causes are. We can do nothing to prevent it.”
Pearce, who is from New Zealand originally, is one of the world’s leading authorities on the spread of asthma but came to the field accidentally and quite late. “I had brucellosis”—a bacterial infection that leaves victims feeling as if they have flu permanently—“when I was in my early twenties, and that sidetracked me educationally,” he says. “I’m from Wellington, and brucellosis isn’t common in cities, so it took the doctors three years to diagnose it. Ironically, once they worked out what it was, it only took a two-week course of antibiotics to cure it.” Though he had secured an honors degree in mathematics by then, he had missed his chance to go to medical school, so he gave up on higher education and worked for two years as a bus driver and in a factory.
It was only by chance, while looking for something more interesting to do, that he landed a job as a biostatistician at the Wellington Medical School. From there he became director of the Centre for Public Health Research at Massey University in Wellington. His interest in asthma epidemiology followed an outbreak of unexplained deaths among young asthmatics. Pearce was part of a team that traced the outbreak to an inhaled drug called fenoterol (no relation to the notorious opioid fentanyl). It was the beginning of a lasting association with asthma, though that is just one among many interests today. In 2010, he moved to England to take up a position at the venerable London School of Hygiene and Tropical Medicine in Bloomsbury.
“For a long time,” he told me when we met, “the dogma was that asthma was a neurological disease—the nervous system sending the wrong signals to the lungs. Then, in the 1950s and ’60s, the idea came along that it is an allergic reaction, and that has pretty much stuck. Even now textbooks say that the way people get asthma is by being exposed to allergens early in life. Basically everything in that theory is wrong. It’s clear now that it is considerably more complicated than that. We now know that half the cases in the world involve allergies, but half are due to something else altogether—to nonallergic mechanisms. We don’t know what those are.”
For many sufferers, asthma can be triggered by cold air, stress, exercise, or other factors that have nothing to do with allergens or what is floating in the air. “More generally,” Pearce added, “the dogma is that both allergic and nonallergic asthmas involve inflammation in the lungs, but with some asthmatics if you put their feet in a bucket of ice water, they begin to wheeze immediately. Now, that can’t be due to inflammation, because it happens too fast. It has to be neurological. So now we are coming full circle for at least part of the answer.”
Asthma is very different from other lung disorders in that it is normally present only some of the time. “If you test the lung function of asthmatics, most of the time for most of them it will be completely normal. It’s only when they have an attack that problems with lung function become apparent and detectable. That’s very unusual for a disease. Even when there are no symptoms present, the disease will nearly always be evident in blood or sputum tests. In asthma, in some cases, the disease just vanishes.”
In an asthma attack, the airways narrow, and the sufferer struggles to get air in or out, especially out. In people with milder forms of asthma, steroids are nearly always effective at keeping attacks under control, but in people with more severe forms steroids rarely work.
