On a dusty August afternoon at a summer camp, 11-year-old Kashaye Gladden joined her friends for a swim in the pond. Afterward the children were hungry and they ran to the air-conditioned dining hall and ate without changing out of their wet bathing suits. A few hours later, when Kashaye started to wheeze, she didn't have any medicine to make it stop. By the time the camp bus dropped her at home, she was gasping for breath. That night Kashaye's grandfather carried her into the emergency room of D.C. General Hospital. It was her third asthma emergency visit in less than a year.
Eight days later Kashaye was still glumly propped in her bed on the pediatrics ward, watching the TV that hung from the opposing wall, her tight braids lying in a tangle on the pillow, her somber brown eyes underlined with dark rings. Kashaye blamed herself.
Asthma came from "being wild, running," she said. Her dream was an athlete's dream -- to become a point guard in the WNBA. At school they called her "Superstar Gladden." But sometimes she got winded in the middle of a game. And here she was back in the hospital, just before the start of school and the season of the Maryland Sparks, her recreation league basketball team. Fall would bring the cold season, with each sniffle threatening to ground her hoop dreams.
"I want to know what do I have to do," Kashaye said as her mother got ready to check her out of D.C. General, "to make it go away."
On the morning that Kashaye came home, 12-year-old Nathan Kingery awoke in his family's washed-brick Chevy Chase home with a slight cold. Nathan, a seventh-grader and a Boy Scout who enjoys reading science fiction and fantasy novels, tried to ignore it. But in the Kingery household, where Nathan is the youngest of four children and the third to suffer from asthma, such events do not go unnoticed.
"One thing I've tried to do is not jump on it right away but let him take the initiative," says Nathan's mother, Betsy. "But it doesn't always work -- because he has a such a high tolerance for not breathing. It bothers me more than it seems to bother him."
Betsy, a psychiatric nurse who works part time, had asthma as a child growing up in Cincinnati and still occasionally wheezes. Her husband, Bill, an international tax lawyer, has bad hay fever. When their eldest daughter, Jessica, was 18 months old she began wheezing and became severely ill. "That was the beginning," Betsy says. During Jessica's early years, the Kingerys were at the emergency room almost every other weekend. When she was 8 years old or so, though, Jessica's asthma stopped. She's 20 now, and a sophomore at Northwestern University. Her sister Megan, 18, was in the emergency room twice for asthma but suffered her last episode at age 3. The disease passed entirely over Corina, 14, but Nathan's congestion and breathing difficulties began when he was only 3 months old.
Still, although Nathan's asthma is more severe than Jessica's was, he hasn't spent a night in the hospital since he was 2 years old -- that's how much asthma treatment has improved in recent years. "With Jessica, they didn't have a lot of the stuff we can treat Nathan with," says Betsy. "Nowadays, if you're aggressive you can stay out of the hospital, and that's sort of our goal."
On this Saturday morning late in a summer blessedly free, due to drought, of pollen, Betsy reaches for the basket of asthma tools on top of the refrigerator in the Kingerys' sunny kitchen and brings down what she calls the "lifeline of asthmatics." It's a large plastic tube shaped something like a kazoo -- a peak-flow meter, which measures the volume of air pushed out of the lungs with a single breath. "If you don't have one of these and you have asthma," Betsy says, "you're not being treated well."
Blow into the meter and the red needle slides up a scale. Each asthmatic has a baseline reading, and the idea is to check the lungs regularly and take action at the slightest sign of flagging breath. When Nathan's readings venture below 80 percent of normal, it means his lungs are gunky and his health is headed south. At around 65 percent, Betsy calls their allergist, Howard Boltansky. He happens to live next door, but they see him at his office near American University.
Colds are the most common trigger of an asthma attack, so incipient cold symptoms -- sniffles, a certain pallor, darkening under the eyes -- warn Betsy that it's time to medicate Nathan. Drugs are key to fighting asthma, but the timing of the drugs is crucial. Which means that someone must be there to notice. "You've gotta know your kid," says Betsy, reciting the mantra of the parents of asthmatics.
More than 5 million children in America have asthma. Their parents make nearly a million emergency room visits every year, which account for half the $2 billion cost of treating children with the illness. Last year about 200 children under the age of 15 died of asthma -- double the number of a decade ago -- and the suffering, worry and disruption in the families of all asthmatics are incalculable.
Then there's the fact that asthma is one of a cluster of diseases, like juvenile-onset diabetes and lupus, that are growing at an alarming rate and stem from complex disorders of the immune system. The Centers for Disease Control and Prevention estimates there were 17.3 million U.S. asthmatics in 1998, compared with 6.8 million in 1980.
Some of that increase reflects the growing awareness and diagnosis of asthma. But not all of it. Asthma has a strong genetic component, but the gene pool hasn't changed in just two decades. Our genes are expressing themselves in an environment different from the one that existed a generation ago. So what are the differences that affect asthma? What have we done to make it so hard for so many people to breathe?
Civilization is somehow to blame -- experts have various opinions on exactly how, whether it's pollution or stress or booming colonies of dust mites or insufficient jolts to the body's immune system. But credit civilization with this: At the same time asthma is increasing, the art and science of asthma care have gradually improved, and are likely to undergo a remarkable change in the next decade thanks to biotechnology. As it is, nearly any well-prepared asthmatic can lead a normal,
active life if -- and this is a big if -- that person has access to good care, and adheres to it.
But good care is a cumbersome, labor-intensive, costly process -- which is why so many financially hard-pressed families end up doing little or nothing until a crisis hits and they must rush their kids to the emergency room. Nathan uses a broad range of premium, state-of-the-art medicines. Just one them, Pulmicort, costs $135 for a container of 200 metered doses, or puffs. Kashaye tends to rely solely on a generic emergency medicine -- the one she ran out of at camp -- which costs $19 for roughly the same number of doses.
A study in New York City this past summer showed that nearly half of all the homeless children in the city suffer from asthma. Another study showed just how drastically different the care is for the rich and the poor: In Spanish Harlem, there were 223 ER visits for asthma for every 10,000 inhabitants; in certain wealthy lower Manhattan districts, there were none.
Still, a raft of recent studies has shown that even poor patients can reduce their emergency room visits if someone takes the time to show them how. Some health plans and hospitals offer such counseling; the American Lung Association brings asthma education to schools. The rules of asthma are not terribly complicated, but they require someone to explain them clearly, and the time and attention of the patient and his or her parents.
"To manage asthma well you need a functioning medical system, society and family," says Peter Gergen, an asthma researcher and doctor who treats kids at the free Clinica del Pueblo in Mount Pleasant. He could write prescriptions for any of the asthma maintenance drugs, but his uninsured patients wouldn't bother to fill them; they can't afford the cost, which, without insurance coverage, could run several hundred dollars a month. So they end up in the ER when a crisis hits.
In 95 percent of all children, asthma is related to allergies, which stem from abnormalities of the immune system. Immunity consists of two interrelated networks -- antibodies, which float through the bloodstream clamping onto foreign particles, and T-helper cells, which marshal the attack against foreign proteins absorbed and presented on the surface of another group of cells known as antigen-presenting cells.
A particular type of antibody, called immunoglobulin E, or IgE, plays a central role in the allergic cascade, the chain of events, riddled with complex feedback loops, that begins when the body encounters a normally innocuous cat hair, or pollen grain, or microscopic dust mite, or whatever, and ends, in the case of asthmatics, with coughing, wheezing and loss of breath.
While we all have some IgE in our bloodstreams, in allergic asthmatics, IgE levels can be many thousands of times higher than normal. When, say, a pollen grain encounters the lung tissue of an allergic person who is sensitized to pollen -- meaning that they have IgE in their lungs and bloodstream that recognizes particular proteins in the seed -- the pollen locks onto IgE particles that are bound to cells called granular leukocytes. That triggers the release of chemicals like histamine, which in turn dilates the blood vessels and constricts the bronchial tubes. A swarm of other chemicals and cells collaborate in the lungs' inappropriately vehement attack on the pollen grain.
If an asthmatic has the right drugs, this cycle can be stopped before it gets far enough along to impair breathing; if he or she doesn't, then the wheezing begins, followed by sagging shoulders, blue lips and the race for the hospital.
Betsy Kingery has the right drugs. In her basket are medications that target various stages in the chain reaction set off by IgE. She's got the bronchodilator albuterol, which targets the end of the chain by relaxing lung muscles tightened by inflammation. She's got Claritin and Benadryl, antihistamines, as well as an epinephrine syringe for the kind of blow-out allergic reaction called anaphylaxis that can kill in no time by causing airways to swell shut. But the most powerful drugs in her basket are the anti-inflammatory corticosteroids: an inhalable powder for daily use, and more potent pills for the bad days. Nathan's baseline peak-flow reading is a little over 300, and this morning he's at 270 -- not bad, but a signal to Betsy that he had better take four puffs of his inhaled steroids today. If his cold gets bad, he'll need to go to steroid pills, a prospect they both find worrisome.
Corticosteroids, first prescribed for asthma in the 1960s, have proved far more effective than any other class of drugs in forestalling the symptoms of the disease. They work by dampening the activity of various immune cells involved in the release of inflammatory chemicals. The problem with these steroids (not to be confused with anabolic steroids, the favored juice of weight lifters and home run whackers) is long-term side effects -- glaucoma, hypertension, osteoporosis and possibly growth retardation. The short-term effects are no bowl of fruit either. "He becomes very, very edgy," says Betsy of her son. "He has difficulty sleeping. He's very hungry. He cries at the drop of the hat."
In the early 1980s the pharmaceutical industry introduced steroid inhalers, which targeted the lungs and therefore pumped less of the drug into the rest of the body, and thus made daily use more feasible. The introduction of inhaled steroids "was like penicillin; it turned treatment of asthma around completely," says Michael A. Kaliner, who for 15 years was director of the Asthma and Allergic Diseases Center at the National Institutes of Health and who since 1993 has directed the private Institute for Asthma and Allergy, at the Washington Hospital Center.
Still, there is some evidence suggesting that even inhaled steroids can stunt growth if used long and intensely enough. Well-informed parents, weighing the risks and benefits, give their children steroids with very mixed feelings. Nathan has been on them since he was 3. "You don't want to use them," says his mother. "But they work. I worry about what I'm putting into his body. But I guess I don't have a choice. I've seen him sick enough that I don't have a choice. When he was younger, I used to think, `Breathing or insanity, which one are we going to do today?' "
Much of the pharmaceutical industry's recent investment in asthma has been aimed at minimizing the amount of corticosteroid needed to provide relief. Until a year or so ago, Nathan used Azmacort, an inhaled mist that came attached to a spacer, a muffler-shaped tube that served as a holding chamber for the medicine while Nathan slowly drew it into his lungs. Then he switched to Pulmicort, a powder formulated specifically to affect lung tissue.
The newer steroids are more effective, and appear to have fewer side effects. In the spring, Nathan started taking a chewable, once-a-day pill called Singulair, one of a different class of drugs called leukotriene modifiers. The hope is they'll reduce his need for steroids.
In sum, Nathan, who stands just under 5 feet and weighs 84 pounds, may end up taking eight different medications on sick days: an antihistamine; oral, nasal and inhaled steroids; inhaled and nebulized bronchodilators; antibiotics; and an anti-leukotriene, which, Nathan says, "tastes like water with too much iron in it."
"Asthma is a manageable disease," says his mother. "But you've got to manage it."
Nathan is, of course, the model patient. "His mom is a nurse, very knowledgeable and stays on top of things," says Boltansky, the allergist. "Nathan is a smart kid and understands what he's doing and why. They can afford the medications, which is a big issue for a lot of people. They come for visits, he gets his allergy shots regularly."
But, Boltansky says, "the Kingerys are not the average of what happens in the real world."
In 1991, and even more emphatically in 1997, an expert panel appointed by NIH stressed the need for corticosteroids in the treatment of asthma. "Asthma, whatever the severity, is a chronic inflammatory disorder," the 1997 report said, and corticosteroids are the most effective anti-inflammatories.
Many asthmatics and many primary care physicians weren't listening. Fewer than a fifth of American asthmatics use anti-inflammatories -- compared with 65 percent of European asthmatics. "I must have given 1,000 lectures to doctors about steroid use," Kaliner says. "Finally I just gave up."
When Eleanor Thornton, a Howard University Medical Center asthma counselor, gives presentations for families or schoolkids, she tries to make three basic points: Know your child; learn your kid's triggers (animal dander, pollen, cigarette smoke, cold viruses, etc.) and avoid them; and deal with asthma's underlying causes by taking steroids or other anti-inflammatory drugs every day, while using bronchodilators -- puffs squeezed from inhalers or breathed through a nebulizing mask -- to relieve symptoms when they occur.
The point is that while tightened lung muscles are the immediate and frightening signs of an asthmatic attack, the underlying cause is usually inflamed respiratory passageways. Without an understanding of this, asthmatics are likely to stop taking steroids because they don't produce an obvious result.
"Corticosteroids don't make you feel better immediately. The emergency medicine makes you feel better but doesn't address the underlying symptoms," says Martha Vetter White, Kaliner's partner at the Institute for Asthma and Allergy, where she directs pediatric research. As a result, "the most important medicine is the one people feel they don't need, so they stop taking it and get into trouble."
Corticosteroids and other anti-inflammatories have not been a part of Kashaye Gladden's regular care. Although she has suffered from asthma since age 2, neither she nor her mother, Kim, knows the difference between preventive drugs like steroids and quick-relief rescue medicine like albuterol.
When Kashaye (pronounced kuh-SHAY) entered the hospital in August, Kim tells a visitor, she was relying on two drugs: albuterol and Proventil. In fact, Proventil is a brand-name form of albuterol, which is also sold as a generic.
To this point, Kashaye's asthma therapy most often has consisted of the following: a puff of albuterol before exercise and whenever she starts coughing. Kim Gladden tries to make sure Kashaye has her inhaler wherever she goes. She made sure Kashaye had it at camp, but neither of them checked it before she went. Kashaye didn't pay it any mind until she felt an attack coming on. Then she went for the inhaler, squeezed -- and nothing came out. There wasn't any medicine in it. So Kashaye did what she always does when the inhaler fails and she suffers a bad attack -- she went to the crowded pediatric emergency room of D.C. General.
Emergency room visits are a sign of uncontrolled asthma. Uncontrolled asthma may lead to scarred lungs, which don't help a young athlete on a fast break. "How many times has she been to the hospital? Wow, man! Fifteen, 20 times?" says her grandfather, Robert Gladden, a brick mason, who usually takes her there. "I can't count them all."
On a warm fall afternoon, Robert and Kashaye and Kim are standing by the cast-iron fence around the Mayfair Mansions, a housing development in Northeast, where Robert and Gloria Gladden raised Kim in the 1980s, a time when the complex was rife with drugs and violence, and where they now help care for Kim's children after school. Urban renewal and community activism have combined to restore tidiness and a measure of peace to the place, which sits in an isolated pocket bordered by the Anacostia River, I-295 and a Pepco plant. Kim wishes she could still live here, but her family has grown too large for the Mayfair apartments.
Asthma's strong genetic component is apparent in Kashaye's family. Her approach to treatment of the disease was inherited, too, a continuation of the way her family has dealt with asthma for three generations -- letting it build to crisis and taking it to the ER at D.C. General.
"I can see it in their eyes and face. They get a look on their face when they get asthma," says Robert. "Kashaye's grandmother had asthma, her uncle had asthma, I had an allergy problem when I was younger. As I got older it sort of went away, but I have trouble breathing every now and then. I think it's a hereditary gene in this family."
"I had it but I grew out of it," Kim reveals.
"When Kashaye's uncle was a baby I spent many a night in the hospital with him," Robert says.
"We'd all go," says Kim.
"I've been carrying 'Shay to the hospital since she was a baby," adds Robert. "I usually stay till she falls asleep." On most visits, the nurses use a nebulizer mask with a stream of bronchodilating medicine to control Kashaye's asthma. If that doesn't work, they admit her. "Usually it's about 1 in the morning when they admit her," says Robert.
The ER visits and overnight stays are a blurred fixture of the Gladden family history. But one or two visits stand out. "One time Kashaye went into convulsions," Kim recalls. "Her fever was about 103. She was shaking out and mumbling something strange, she was screaming. Oh, she scared me to death." Kim was nine months pregnant on that occasion. She slung Kashaye on her back and ran down the sidewalk until she found her half-brother Wayne, who got Robert, who drove them in.
Kim recalls the exact date of that attack because she went into labor at the hospital. She gave birth the next day -- September 26, 1994 -- to Kashaye's youngest sister, Blakeney, while the doctors cared for Kashaye in a room across the blacktop parking lot.
The truth is, Kashaye's care could easily be better -- and her basketball game enhanced -- if her family had a plan for dealing with her asthma and the wherewithal to stick to it. Kim has missed work and once even quit a job in order to better care for Kashaye, the only one of her five children with asthma. These days Kim works two jobs to help support the family -- as an apprentice telecommunications electrician and as a weekend security guard at Voice of America. That job until recently gave her medical insurance; now she says she is relying on Medicaid. Kashaye's father, Shante Jordan, is a long-distance truck driver who's on the road a lot.
At Neval Thomas Elementary in Northeast, where Kashaye and her siblings attend school a block from their grandmother's house, her best friend warns her not to run too much and some of the adults are attuned to her asthma, too.
Sonsyrea Tate, author of the memoir Little X: Growing Up in the Nation of Islam and a long-term substitute teacher in Kashaye's fifth-grade class last year, says she worries that if asthma keeps Kashaye from playing basketball, it will take the drive out of her life. "She's a wonderful child, with a strong work ethic and good study skills, and at times I thought asthma only made her more motivated," says Tate. "But when she had an attack at the end of the year, I was worried she wouldn't be able to play basketball, because it was clear that the basketball affected her life in so many other ways."
Millicent Collins, who directs the pediatric emergency room at D.C. General and has worked in it for 20 years, sees children like Kashaye every day. The severity of the asthma she sees is increasing. In the past three years, two asthmatic children have come in breathless and blue, and died at the hospital -- "they were essentially DOA," Collins says.
A multitude of factors conspire against poor asthmatic children. Many of them have regular primary care physicians who are leery of prescribing steroids, or too busy to deal in appropriate depth with the situation. The best allergy clinics dedicate two or three hours to a patient's first visit -- the time required to thoroughly check history, lung function and allergies, and to follow up with education to help the patient or parent become a participant in care.
Managed care has a mixed record here. Some companies, recognizing the long-term savings, have encouraged asthmatics to get regular treatment and, it is hoped, avoid emergency rooms. Others are criticized for putting up unnecessary roadblocks to patients who need regular visits with an allergist. While a good pediatrician can keep up with asthma much of the time, allergists and lung specialists can be necessary in treating severe or complicated cases.
"In the days when we didn't have treatments for asthma, the pediatrician would send you to a specialist when they didn't know what to do," says James P. Kemp, president of the American Academy of Allergy, Asthma and Immunology. "Now, the pediatricians can't keep up with all the new treatments, but they aren't allowed [by health plans] to send you to a specialist."
Often, though, Collins believes, the key factors limiting good treatment are societal. The patient "can't get a taxi, or somebody has to watch the baby, or they don't have the co-pay to buy the pills. Social problems. And no one follows up."
"I blame myself," says Kim Gladden, as she toys with a peak-flow meter that the staff at D.C. General has given her daughter -- the first time the Gladdens have ever had a $20 peak-flow meter for home use. Kim also hopes to get a $200 home nebulizer for treating emergencies -- and to take Kashaye to an allergist for the first time. When she was little, Kashaye liked the attention she got at the emergency room -- friends and relatives bearing treats, nurses and doctors hovering. But no more. "She doesn't like being sick," says Kim. Now, she adds, "I'm just getting all this stuff together."
In a cramped warren of offices at the Washington Hospital Center, Michael Kaliner and Martha White see patients ranging from wealthy diplomats to the humblest immigrants, from employees covered by posh PPOs to Medicaid patients. "We're
NIHers," says Kaliner. "We'll see anyone." They are also among the most distinguished practitioners treating asthma in the country and between them have about 500 publications, scores of consultations and research projects run in conjunction with big pharmaceutical firms.
As researchers, Kaliner and White can see that science is homing in on the causes of asthma and is beginning to come up with therapies that may make it easier to treat -- if not cure -- asthmatics in the future. Both preach the gospel of anti-inflammatories and decry the societal and health care obstacles that make it hard for patients like Kashaye to get good care.
But when it comes to the bottom-line question -- why is asthma increasing in America? -- they tend to disagree.
Kaliner, a Baltimore native who has spent 30 years treating asthma, gives the simple answer that's also the one most closely supported by evidence. It also happens not to be a terribly sexy answer. "The increased number of pets," says Kaliner. "Over the past several decades, allergies, asthma and households with pets have increased in a direct correlation with one another. There's been a tenfold increase of each in this century."
Until the 1980s many people blamed air pollution for rising asthma rates, Kaliner explains. But the number of dirty particles in the air has been falling (with the notable exception of diesel fuel exhaust, which has been linked in some studies to asthma-related changes in immunity), while asthma has skyrocketed.
Now, the basic explanation for increased asthma rates goes like this: The more we have centrally heated and cooled our homes, and padded them with carpets and allowed our children to spend more time inside them, watching TV instead of running around in the fresh air, the more they have been exposed to various asthma-triggering allergens -- cat dander, cockroach feces and dust mites being the major culprits. What has made homes cozy for humans has made them cozy for critters -- "snug as a bug in a rug" has taken on a sinister connotation.
In recognition of this threat, many asthmatic families use high-powered air filters and vacuum cleaners, while tossing out the rugs, dogs and cigarettes and dosing their kids with plenty of antibiotics. They seek an ideal of cleanliness and simplicity. The underlying idea is that asthma is a disease caused by filth, or at least certain types of filth.
Paradoxically, there's another school of thought about asthma, which can basically be boiled down to the opposite: Asthma is a disease that could originate in too much cleanliness. This is what White believes.
White, a slim Virginian who thinks fast and talks and moves at birdlike speeds, has just finished a routine consult, a college kid who found himself short of breath after exercise. Today's patient stopped taking his inhaled corticosteroids some weeks ago, thinking he didn't need them. His lung function test, at 68 percent of normal, shows he was wrong. White has told the guy to get back on his steroids, and sends him away. He's a big boy, and the advice should stick -- adults have the power to comply if they wish.
"The thing about children," White says, back at her desk two partitions away from Kaliner's, "is that they have far fewer choices in the company they keep." Cigarette smoke from a parent can be a trigger of asthma (Kashaye's grandmother smokes -- "only in the back rooms," Kim Gladden says). Children who have allergies are 10 times more likely to get asthma if they are exposed to cats as infants -- and four more times likely to get asthma if exposed to lots of dust mites. The point is that something in early exposures can determine whether you get severe allergenic disease, White says. It's a question of programming.
This, as it turns out, is a way of backing into the question of "Why is asthma increasing so much?"
In the past decade, research on mice (and some on humans) strongly suggests that while people start out life with roughly equivalent immune cells, in some a switch gets thrown that creates immune systems prone to allergy and asthma. Immune bodies called T-helper cells provide the key stimulus and feedback in this loop: If you've got the normal type of helper cells in your lungs, scientists describe your immune system as a Th1 type. If they're abnormal, it's Th2. We begin life, apparently, with unprogrammed T cells -- Th0. What throws the switch to Th1 or Th2 isn't known -- there are clearly genetic and environmental influences. But there's nothing inherently evil about cat dander. The body develops an overblown response to it because its programming is set wrong.
In 1997, a scientist named Taro Shirakawa published a controversial paper in the journal Science that studied asthma rates among Japanese kids exposed to the bacteria that causes tuberculosis, and found that the kids whose immune systems had reacted to fight off the bacteria usually didn't get asthma. Another study showed that African children who had gotten measles had lower rates of asthma than those who didn't. Other data showed that younger siblings, and children in day care at an early age, had lower rates of asthma.
The message from these studies was that early exposure to certain kinds of germs seemed to be beneficial to the immune system, at least in regard to allergies. Thus, the paradoxical "hygiene hypothesis." The more scrupulous the hygiene, that is, the unhealthier -- in asthma terms -- the child.
Early infections, goes this theory, prime the immune system for a healthy Th1 response, ideal for attacks on viruses and bacteria. The absence of early infection, at least in genetically predisposed individuals, leads the immune system down the abnormal Th2 road to the manufacture of IgE, which attacks cat dander. Which raises the question, for some, of whether the blanket use of antibiotics and vaccines, in keeping children free of severe infections, may in part be causing the upsurge in asthma. Says Martha White, "It's a possibility."
IgE sets off an allergic chain reaction in the human body like a detonator for dynamite. It was discovered in 1967, and within a few years scientists had tricked out how it interacts with immune cells to produce inflammation. But it wasn't until 1994 that scientists discovered the precise chemical sequence of the site where IgE binds to these cells.
This opened up new possibilities for asthma treatment. If bronchodilating sprays targeted muscle spasms -- the end of the road of the asthma cascade -- and steroids were what one government researcher called "the buckshot approach" to combating asthma, IgE could be the target for a silver bullet that fires much higher up on the causal chain of asthma.
Kaliner and White have done clinical trials with a substance called anti-IgE, which is derived from mouse cells, and they both see it as a promising new therapy. "It could put us allergists out of business," White says, half in jest. "We've had patients who not only recovered from asthma, but lost food allergies as well."
The biotech company Genentech, in partnership with the pharmaceutical giant Novartis, is planning to seek Food and Drug Administration approval in May for an anti-IgE therapy.
From an intellectual perspective, what's most interesting about anti-IgE is that it serves as what one scientist calls a "proof of concept" -- its effectiveness proves that IgE plays a crucial role in asthma. Anti-IgE therapy is designed to reengineer the human body, re-adapting it to conditions that humankind itself created. IgE appears to have evolved as a means of driving a powerful immune response to certain types of parasites. But people living in cities, particularly in the developed world, don't get parasites anymore.
"When we were amphibians crawling around in the primordial ooze it was important to have IgE to keep parasites from killing us," says Robert Fick, the Genentech scientist directing the anti-IgE project. "But for the vast majority of people in the world, now that we're not crawling around in a sea of parasites, IgE causes disease."
Kaliner speculates that higher asthma rates among some minorities could partly be attributable to this evolutionary connection: Because parasites have always been more prevalent in tropical climates, evolution may have selected for high-IgE carriers among the African and Hispanic ancestors of people now living in the United States.
As promising a treatment as anti-IgE could be, trials on 1,200 people have shown that when they stop receiving monthly injections of it, allergies and asthma return. That's why an even more experimental therapy, a possible anti-asthma vaccine, is generating excitement among asthma researchers. This new approach, in early trials now, combines allergens such as dust mite proteins with snippets of synthetic bacterial DNA.
"The idea is to trick the immune system into thinking, `You dummy, this isn't an allergen, this is a bacterial protein -- see, it's got bacteria DNA attached to it, and you should respond accordingly,' " says Arthur Krieg, an Iowa rheumatologist who made a key discovery that helped fuel this new DNA effort.
"This is a quantum leap in terms of immunotherapy," says Lawrence Lichtenstein, director of the Johns Hopkins Asthma and Allergy Center. "I've been at this for 40 years and nothing has come along like this up to now." Lichtenstein is a consultant to a company, Dynavax, that is awaiting FDA approval to try its version of the vaccine on people.
Last month, British immunologist Stephen T. Holgate reported a successful trial of a similar vaccine on 12 asthmatic patients at Southampton General Hospital. When exposed to dust mites that normally triggered their asthma, two-thirds of them had no reaction. Which could be good news for Kashaye Gladden and Nathan Kingery.
On the last free Friday before school starts, Nathan is receiving a shot -- not a vaccine, just an allergy shot -- that is part of the tedious immunotherapy he is undergoing in an effort to gradually dull his response to allergens. Bravely, with barely a wrinkling of the nose, he stands steady while a nurse injects him with a 1-in-500 dilution of mite mix, horse dander and tree and ragweed pollen in one arm. Then he gets another shot, in the same dilution, of molds, mildew and grass and weed pollen in the other.
Nathan has to go in every week to receive minutely increased concentrations of the allergens with the intention of desensitizing himself. If he misses a week because he's sick, or on vacation, or whatever, he has to start all over again at the lowest concentration.
Sitting in the waiting room -- a 15-minute wait is prescribed to make sure he doesn't react to the shots -- Nathan takes the opportunity to fire a few questions at Boltansky.
"My mom wants me to ask, do you think it would be possible for me to cut down on my inhaled steroids?"
"How many puffs are you doing now?" Boltansky asks.
"Four daily, two each morning and night."
"How much rescue medicine?"
"Not at all."
"How was your breathing on the peak flow?"
"I got a 95."
"Okay," Boltansky says, "you can go to three puffs once a day. If things stay good, in a few weeks we'll go to two puffs once a day. All right?"
Nathan nods, satisfied, and goes back to his novel.
"What we consider state-of-the-art treatment today is dramatically different from what it was 10 years ago," says Boltansky. "I think it's going to change even faster in the next five or 10 years. I think it will be neat to see."
Of course, all the dreams of new therapies could turn to nothing. Drugs tend to work best in trials because of the placebo effect, and this is particularly true of drugs for asthma, which has a large psychosomatic component. "The best way to treat an asthmatic of any severity is to put them in a clinical trial," says Homer Boushey, director of immunology at the University of California at San Francisco, who has been running clinical trials of anti-IgE therapy.
Maimonides, the 12th-century rabbi, philosopher and physician, reportedly got good results treating asthma with chicken soup. Kashaye's uncle Torrance was told years ago by a doctor to guzzle warm ginger ale when he felt an attack coming on, and he hasn't had an attack since, according to Robert Gladden.
Which may partly explain why Karen Kent, Kashaye's pediatrician, is hesitant to refer her to a specialist. Yes, it's true that Kashaye has moderate-to-severe persistent asthma and neglects her care, Kent says. And it's true that Kent's primary care medical center lacks the pulmonary function testing equipment needed to set a baseline for asthma care. It's also true that Kent is able to provide only 20 minutes for an asthma patient, while Kaliner and White set aside up to three hours for the first consult.
In another year or two, Kashaye may be ready to take control of her own care, Kent hopes. In the meantime, Kent hasn't scheduled her for another appointment, although she'd like to try Kashaye out on Singulair, the daily anti-inflammatory pill that seems to be working for Nathan.
But Kent has the feeling that Kashaye and her mother only pay attention to Kashaye's asthma when she's sick, so there's no point teaching them the often time-consuming preventive care at the moment. "There are so many factors to teach in asthma care that to get parents who are nonmedical to focus on subtle symptoms is pretty difficult," she says.
Which means that in all likelihood, the next time a doctor sees Kashaye, she'll be almost entirely out of breath.
Arthur Allen last wrote for the Magazine about a celebrated "eugenic baby" of the 1920s. He'll be fielding questions and comments about this article at www.washingtonpost.com/liveonline on Monday at 1 p.m.