When the Match Is Half Full

New drug strategy vastly expands pool of potential blood marrow donors.

For years, bone marrow transplants have proved their mettle as a remarkably effective way to treat—even cure—certain types of cancers and genetic diseases.

But the healthy donor tissue needed for the transplants has had to closely match the patient’s tissue. Absent that match, the body’s immune response gears up to reject the new tissue, or the new healthy tissue can attack the recipient in graft-versus-host disease (GVHD).

Complicating the situation even further, finding a proper match could take months, which is time that most patients who need a transplant don’t have.

Today, however, new research here is making it possible to transplant tissue that isn’t a close match, without launching the potentially deadly side effects that would have been a risk only a few years ago. "Patients up to age 75 now have nearly a 100 percent chance of finding a match,” says Richard Jones, director of Hopkins’ Bone Marrow Transplant Program.

In the past, donor and patient tissue had to have in common all 10 of the human leukocyte antigens that indicate the likelihood of tissue rejection or GVHD. But even in siblings, there’s only a 30 percent chance that all these protein markers will match. And though millions of potential marrow donors have signed on with international registries, the chance that a patient of northern European descent will find at least one nearly complete donor match is still only about 50 percent to 60 percent. For some ethnic groups, the odds are much lower.

Using immunosuppressant drugs to stave off the recipient’s immune response has allowed physicians to transplant tissue from donors with as few as half the protein markers being a match. The problem: This approach leaves already vulnerable patients immuno-compromised and at serious risk for other illnesses.

So Jones and his colleagues have put a new spin on the established practice of administering the anticancer drug cyclophosphamide in high doses before a transplant. "Cyclophosphamide has been the most commonly given drug before bone marrow transplants because it has a powerful antitumor effect, and it is also a powerful immunosuppressant,” says Jones.

"Now we also give cyclophosphamide after the transplant.” This strategy takes advantage of the time when the T-cells lining up to attack the mismatched tissue are especially vulnerable. And not only does post-transplant administration of cyclophosphamide target the problem T-cells, it doesn’t wipe out the whole immune system in the process.

Oncologists at Johns Hopkins have now completed about 250 of these half-matched transplants, including, says Jones, about 65 last year alone—”the most anywhere in the world."
Mary Ann Ayd

Bringing Back Pre-Pen

When a key allergy test disappeared, Frank Adkinson and company got to work.

Says Adkinson: “I certainly never expected to be in the ‘orphan drug’ manufacturing business.” Photo by Keith Weller

Imagine being sick with a deadly bacterial infection and being denied the same effective, safe, and inexpensive antibiotics that the vast majority of other people can take. That’s the case for tens of millions of patients in the United States with a history of penicillin allergy. Not only must these unlucky patients avoid penicillin, but also the 40-odd other antibiotics in the same drug family—forcing them to turn to other antibiotics that are often less effective, more toxic, and much more expensive.

A saving grace for penicillin allergy patients came in the 1960s, with a skin test to determine who was truly allergic to this family of antibiotics. This new tool brought a surprising discovery: The vast majority of patients who had once experienced an allergic reaction to penicillin were no longer allergic.

"For 35 years, we’ve known that patients can lose their penicillin allergies over time. Using the skin test can remove the penicillin allergy label for 80 to 90 percent of people who were ever told that they shouldn’t take these drugs," says L. Franklin Adkinson Jr., a professor in Allergy and Clinical Immunology at the School of Medicine.

“We put up money from the mortgages on our houses, and we had to borrow a lot. Even though our spouses knew that this was a worthwhile venture, they thought we were all nuts.”

Like most of his allergist colleagues, Adkinson had come to rely on the penicillin skin test, known as Pre-Pen, as a given for patient care and allergy studies. Then, out of the blue, the sole company that manufactured Pre-Pen in the United States pulled the product off the market. Costs for maintaining the FDA’s strict manufacturing requirements, along with a small market compared to other pharmaceuticals, made this test extremely unprofitable to manufacture. Within six months, the world’s only other manufacturer, based in Europe, came to the same decision. By 2004, all existing supplies were gone.

"The two major sources of this product worldwide just disappeared. My colleagues and I thought this was completely unacceptable, and we wanted to do something about it," Adkinson says.

So he and a handful of other allergists—including pediatric allergist Louis Mendelson and his University of Connecticut pharmacology colleague Charlotte Ressler, as well as James Wolfe, affiliated with Stanford’s School of Medicine—got to work.

They learned that the company holding the rights to the test was willing to turn over all the information necessary to make Pre-Pen to whoever would carry the manufacturing torch. So the four researchers began by shopping around the idea to drug manufacturers already making penicillin. After more than two years of fruitless searches, they were nearly willing to throw in the towel. That’s when they dreamed up what seemed to be a pie-in-the-sky idea: Why not become Pre-Pen manufacturers themselves? As physicians, they lacked the intimate knowledge of the complicated FDA regulatory issues that drug manufacturers need to satisfy. They also needed capital—and lots of it. So they recruited consultants: one an expert at FDA regulations, and the other an authority on building manufacturing facilities up to code. Then they scraped together money from wherever they could find it. "We put up money from the mortgages on our houses, and we had to borrow a lot. Even though our spouses knew that this was a worthwhile venture, they thought we were all nuts," says Adkinson.

By early 2007, the quartet had bought a small building in a business park in Plainville, Conn., and begun outfitting it with equipment. Within a couple of years, that warehouse was transformed into a sophisticated drug manufacturing facility. Their FDA application to manufacture Pre-Pen was approved on September 26, 2009, and they started production shortly afterward.

Nowadays, their facility is manufacturing Pre-Pen at full speed, and patients can once again have access to the pivotal test that can tell them whether they’ll be able to take one of the world’s most tried-and-true antibiotics.

"We’re able to tell patients once again with a high degree of confidence whether they’re allergic to penicillin," says Adkinson. "It really makes a difference in their lives, and in the public’s health."
Christen Brownlee

No Worse for Wear

Bressler and colleagues used fluorescein angiography to tease apart a presumed case of cause and effect. Photo by Keith Weller

For years, it’s been thought that patients with both cataracts and earlier stages of age-related macular degeneration (AMD) presented the proverbial no-win situation: Operate to remove the cataracts and you risk accelerating progression of AMD.

Now, thanks to the results of an innovative study by Wilmer’s Neil Bressler and colleagues, ophthalmologists can feel far more sanguine about proceeding with cataract surgery in these patients.

To tease apart presumed cause and effect, Bressler—an AMD expert who heads the Wilmer Eye Institute’s Retina Division—and his group used fluorescein angiography to examine the macula in 86 patients with confirmed AMD just prior to cataract surgery. They also obtained images at one week, three months, and one year after surgery to document postoperatively any growth of new vessels (advanced wet AMD) that can cause further retinal deterioration and vision loss.

The imaging showed progression to wet AMD in eight eyes at one year following cataract surgery. However, this wet AMD already was present one week after cataract surgery. Based on the size of the vessels and other features, Bressler says, the researchers concluded that wet AMD likely was present but undetected prior to cataract surgery.

Cataracts and AMD can occur simultaneously, and because some wet AMD is very subtle, says Bressler, even with angiography, "physicians might miss it because the cataract blocks adequate visualization [of the retina]." That could help explain the "presumed progression" of AMD after cataract surgery, he notes.

The good news: Wet AMD developed in only three eyes at one year following cataract surgery when angiograms one week after cataract surgery had confirmed its absence—a progression rate of less than 5 percent. That’s within the expected rate from past studies and similar to that among patients whose other eye was not operated on for cataract during the same period.

Although the next step is to find a way to better determine existing wet AMD before cataract surgery, says Bressler, "we’re now more confident that cataract surgery doesn’t worsen AMD." Mary Ann Ayd

You’ll Get No Kick From Cocaine

Vaccine shows promise in blunting tough-to-beat addiction.

What if there were a safe and lasting way to block the high that users get from cocaine, no matter what form—injected, snorted, or even the potent inhaled drug called crack?

That possibility came a bit closer this summer, when Hopkins began trials of a prototype cocaine vaccine with 50 active cocaine users—men and women who say they want to quit. Some 300 will participate nationwide.

Led by Maxine Stitzer and Andrew Tompkins, with the Behavioral Pharmacology Research Unit, the team is one of six nationally to conduct phase II trials of the TA-CD vaccine. Ideally, the vaccinations will jog subjects’ immune systems to create useful antibodies—those able to pick off cocaine molecules before they cross the blood-brain barrier to stimulate dopamine-based reward circuits in the brain.

Stopping cocaine’s effects completely could bring a sea change in recovery strategies, the researchers say. But even if the vaccine merely blunts the high, that might tip the balance enough to make existing tactics more effective.

The studies follow a decade of animal research and then a sentinel inpatient vaccine study of cocaine users. "Even before it appeared in a journal last fall, the results of that inpatient trial caused a stir in the research community," says Stitzer. "It was the first time a treatment substantially reduced the subjective effects of cocaine. After literally years of seeing negative trials, this would be hard to overlook.

"That said," she adds, "we know there are still challenges." The anti-cocaine antibody levels, for example, fade within a year, making booster shots necessary. In a larger outpatient study, just half of fully inoculated people produced enough antibodies to dull cocaine’s effects. Still, Tompkins points out, the possibility of helping even that many motivated cocaine users is highly significant for a life-sinking illness that affects millions.

He also takes heart in the potency of the vaccine for those who are affected by it. "It appears to damp down even crack cocaine," Tompkins says, "which travels the fastest to the brain."

Unlike other addictive drugs, cocaine has thumbed its nose at 30 years of concerted searching for a medication to stop dependence. The same is true for its amphetamine cousins and the other stimulants. There’s no methadone-equivalent, as exists for heroin or other opioid addictions. Much of the problem, Tompkins says, stems from the stimulants’ intimacy with normal brain circuitry: "That makes it difficult to find an agent that blocks the drugs while leaving important brain function intact."

In the ongoing trials, it will take several injections of vaccine to get the anti-cocaine antibody titer as high as necessary. The physiology and safety will be under study, but researchers’ eyes will linger longest on the urine tests and written surveys that will flag a hoped-for drop in cocaine use. If the trials are successful, says Stitzer, the vaccine would be a candidate for FDA approval, and then, ideally, tailored to community use. Marjorie Centofanti

Reducing Open- Heart Surgeries

No cutting with new pediatric valve repair procedure

Ringel’s heart procedure starts in the leg. Photo by Keith Weller

Open-heart surgery is no stranger to patients like Alex Compton, 17. Born with tetralogy of Fallot, Compton has endured several invasive surgeries with long hospitalizations and recoveries, most recently when he was 8 and needed his pulmonary valve repaired. It meant 10 days in the hospital.

This past May, Compton needed another pulmonary valve repair. But this time, a minimally invasive approach required only a one-night stay. Two days later, he attended rehearsal for his high school graduation.

The new catheter procedure is called percutaneous pulmonary valve replacement, and Johns Hopkins pediatric cardiologist Rich Ringel is one of a handful of interventionalists nationwide who perform it. "There is no surgery, no cutting of anything," he says.

With the patient under general anesthesia, Ringel places a stent-mounted bioprosthetic valve onto a balloon-tipped catheter and threads it through the leg’s femoral vein and up to the pulmonary valve. He then expands the bioprosthetic valve to prop open the poorly functioning existing valve.

Ringel explains that in patients with left-sided congenital heart disease, surgeons typically replace the aortic valve with the patient’s own pulmonary valve, which in turn is replaced with a cadaveric pulmonary valve. But over time, the cadaveric valve—known as a "conduit"—scars and narrows, requiring another valve replacement through open-heart surgery.

"When the surgeon puts in a conduit," says Ringel, "we hope that it will last 15 or 20 years. But too often it lasts only a few years. So we insert this valve in the hope of giving that conduit the years it was designed to get and to reduce the number of open-heart surgeries patients need over a lifetime."

The procedure, says Ringel, has proved successful enough in U.S. and European trials for the FDA to approve the valve as a humanitarian-use device for patients like Compton. Gary Logan

A Window Into MS

Retinal scanning technique offers new insights into disease’s progression.

OCT scanning, says Calabresi, is “ready for prime time” in multiple sclerosis. Photo by Keith Weller

"It’s one of the great frustrations in treating patients with MS," says neurologist Peter Calabresi, head of Hopkins’ Multiple Sclerosis Center. "You get a high-quality scan. You see the white spots that signify lesions in the brain. But that doesn’t always correlate with what you see happening to your patient."

An MS patient could, for example, have neuralgia’s electric shocks running down both arms and suffer the numbing fatigue of a flare-up, yet clinicians might see no change from the last imaging.

This paradox isn’t unusual, says Calabresi. And not only can it make it challenging for physicians to know how aggressively to treat the disease, but Pharma companies are less likely to invest the millions needed to test new drugs because it’s so hard to verify their effects in a reasonable time.

The problem is that lesions don’t always define the underlying pathology in MS. Calabresi and his colleagues, however, are finding ways around that. One method, optical coherence tomography (OCT), is newly pulled from ophthalmic clinics where it’s used to assess retinal damage from glaucoma or macular degeneration. Now OCT is poised to turn the eye into an easy, reliable window on MS. "It’s ready for prime time," says Calabresi.

In an OCT scan, a beam of infrared light plays across the retina, and the resulting data on the "bounce-back" get crunched by a microprocessor into a meaningful readout. It’s like ultrasound, only with light. Within 10 minutes, in the comfort of a neurologist’s office, Calabresi says, you can measure the thickness of the retinal nerve fiber layer. And that’s becoming a valuable metric for him and his colleagues.

"Originally, we used OCT just to assess the optic neuritis that’s common with MS," he says. But there’s been a sea change in the way medicine views MS, with the realization that the lasting damage comes from neurodegeneration as well as autoimmune attacks on myelin. So Calabresi and colleagues can track a patient’s thinning retina as a finger on degeneration’s pulse.

He and colleagues on a select multicenter team have, for five years, followed MS patients with OCT. They’ve shown, for example, that the retinal layer thickness is in sync with how patients do on clinical tests of vision loss—a true structure-function link. They’ve also found that the more progressive the MS, the more rapid the thinning.

Most important is that Calabresi’s team showed a significant tie between retinal changes and increased brain atrophy, the MS hallmark. "These matches," he says, "are better than we could have hoped for. We’re at a point where we’re using OCT cautiously in clinical practice. We have the newest generation machine. Its resolution is spectacular."

Calabresi cautions against dismissing the usefulness of MRI, however. Great strides have been made recently with that method, particularly with diffusion tensor imaging. "It’s important to be able to check the integrity of entire nerve fibers," he says. "What we hope is that both techniques will help predict who’s going to have brain atrophy. Then we might intervene before the brain is greatly affected." Marjorie Centofanti

The Assist After Surgery

For people with high-risk hearts, a better way to avoid medication downsides.

Although not all patients are candidates, Ashish Shah and colleagues are encouraged by the possibilities that are opening up. Photo by Keith Weller

To sustain a high-risk heart patient during the first days after surgery, Ashish Shah has found a tactic to believe in. In recent months, the cardiothoracic surgeon has employed the latest thinking in how to assist a recovering cardiac muscle without flooding the rest of a weakened body with taxing medications.

"We’re getting away from chemically supporting these patients’ hearts," says Shah, whose work in cardiac surgery is complemented by his primary specialty as the surgical director of Johns Hopkins’ lung transplantation program, "and moving toward mechanically supporting their hearts. It’s better for the rest of the body."

The new approach draws on recent advances in cardiac assist devices that make them an appealing alternative to the usual array of medications aimed at easing the postsurgical transition. The medications may be good at improving a weakened heart’s pumping ability, says Shah, but they can exact a toll on untargeted organs, such as the kidneys, liver, and brain.

And, as is too often the case, he says, many late-stage cardiac patients already have compromised kidney function, which magnifies the risks. "In the past, we really didn’t have good ways to maintain these people medically," says Shah, "so they either died or were refused surgery."

“In the past, we really didn’t have good ways to maintain these people medically.” – Ashish Shah

Johns Hopkins has long been successful using left ventricular assist devices, which are connected to patients’ hearts in an open procedure that has allowed patients to live long enough for heart transplants. The LVADs also sometimes serve as destination therapy, extending lives when transplant is not an option.

But, in what Shah calls a paradigm shift, the newer technology offers its own prospects because it’s moved away from the pulsatile method of pumping blood to a more continuous flow approach. Small—only 5 to 6 millimeters at its widest—and driven by an external power pack about the size of a netbook computer, it can be threaded via catheter up through the femoral artery in a matter of minutes. It uses magnetically levitated propellers to drive blood flow, makes virtually no noise, and generates almost no heat.

Shah, cardiac transplant surgical director John Conte, and heart failure director Stuart Russell give two examples of patients they’ve helped with the new option. One man, who has severe kidney disease, needed bypass surgery and a mitral valve repair. By using the short-term mechanical support to maintain blood flow to his kidneys, they were able to avoid giving him high-dose medications, and he made a complete recovery without further kidney injury.

Another patient was in profound shock and required emergent bypass and mitral valve surgery. But after the operation, even when he was receiving maximal medications, his cardiac function would not sustain him postoperatively. Shah placed a new-generation Impella pump, and the patient recovered over the following week.

Both patients are alive and well.

Though Shah describes the new device implant procedures as easy, he believes the ideal candidates must be chosen in a way that’s "up front and thoughtful." The intention, he says, is to use the technology only for short durations, from perhaps three days up to a full week. Patients need anticoagulation therapy while the device sustains them, which puts them at increased risk for bleeding and stroke. So far, says Shah, the devices appear to produce very negligible clot material. Ramsey Flynn

How to Mend a Broken Voice

Teachers, lawyers, and others who put a premium on talking can find their voices just give out.

Lee Akst believes most patients with voice complaints, including those with phonotraumatic lesions, can be helped. Photo by Keith Weller

Most people imagine voice patients as opera singers or actors. But the reality is that most patients with voice complaints work more routine jobs—as lawyers, salesmen, and schoolteachers, says Lee Akst.

"A classic voice patient is someone who uses their vocal cords so much that they’ve developed a lesion on them that gets in the way of good vocalization," explains Akst, a laryngologist. And schoolteachers are especially subject to such injuries. It’s a population—along with the marketers and lawyers and other highly vocal professionals—that Akst plans to treat as he takes the helm of the Johns Hopkins’ Division of Laryngology. Most importantly, however, he wants to grow the division and the breadth of services it offers. And he’s primed to do exactly that.

Akst, who specializes in voice and swallowing problems, joined Hopkins from Chicago’s Loyola University Hospital, where, as director of laryngology, he helped establish a center for voice and esophageal disorders. Now he’s doing the same here, joining together with current otolaryngology faculty and staff and bringing them all under the umbrella of the newly established Johns Hopkins Voice Center, in the outpatient center of the hospital’s East Baltimore campus.

"We really want to expand the variety of specialty services we’re offering patients with these issues," Akst says. Those patients tend to have one major thing in common: They must frequently use—and sometimes strain—their vocal cords.

"Teachers are particularly high risk because they’re constantly talking and projecting their voices to the classroom, and they’re unable to rest their voices when they’re feeling tired or hoarse," Akst says. "They have to keep pushing through in order to communicate with their students."

Over time, he continues, their voices—and those of others in vocally demanding jobs—just give out.

Fortunately, he says, most patients with voice complaints can be helped, especially if diagnosis is early and accurate. Patients with phonotraumatic lesions such as nodules, polyps, and cysts can benefit from voice therapy and also surgery. Patients with growths on their vocal cords, like cancer or papilloma, can benefit from surgery as well, often through procedures that use advanced pulsed laser technologies to help preserve voice. For patients with vocal cord paralysis, there are medialization procedures and also injections that can help restore voice.

"There’s always something we can do," Akst says. "We can always make someone at least a little bit better." Lauren Manfuso

Why That IBD Prescription May Not Be Working

“Any time you have a chronic disease, the adherence rate drops,” says Sharon Dudley-Brown. Photo by Keith Weller

For half of her life, the 60-year-old had suffered from ulcerative colitis. Despite having been prescribed mesalamine by her local gastroenterologist, she still had frequent bouts of pain and diarrhea.

Her flare-ups finally brought her to Johns Hopkins, where she met with Sharon Dudley-Brown, a PhD nurse practitioner who specializes in helping patients who have inflammatory bowel disease to follow drug regimens. Dudley-Brown sat down with the woman to try to figure out what was wrong—and the answer was discovered almost immediately.

"She told me she would take her medication whenever she was having problems," says Dudley-Brown. "When I explained that she needed to take her medication every day, regardless of how she felt, she replied, ‘Nobody ever told me this.’"

Dudley-Brown’s ability to improve adherence to IBD medication regimens stems in part from her research on and experience with the reasons patients don’t take their medications. Among them are demographics (young patients are less adherent), the complexity of the regimen, and the level of pain (or symptoms) the patient experiences.

The best chance to achieve adherence, Dudley-Brown finds, comes from engaging patients as people. "If you give them the opportunity to communicate and make it clear that you’re not going to bite their head off if they tell you they’re not taking their medication," she says, "they’ll tell you the truth." Geoff Brown

Not Like Everyone Else

Emotional support is key when treating girls with rare malformation.

Lisa Kolp specializes in repairing reproductive tract abnormalities. Photo by Keith Weller

Almost all young women diagnosed with vaginal agenesis (the absence of a vagina) have never heard of it, and few pediatricians think to look for it. A congenital disorder of the reproductive system, it affects roughly one in 5,000 females. It occurs when the muscular canal connecting the cervix to the vulva stops developing.

"Girls who are 13 or 14 are shocked to find out they don’t have a vagina, and even more stunned if they learn they don’t have a uterus," says Hopkins gynecologist Lisa Kolp. "They’re often angry and frustrated and wonder why they can’t be just like everyone else. That can lead to some intense, emotional ups and downs."

Typically, the condition is diagnosed when a girl enters puberty and fails to begin menstruating. Those patients who retain a uterus may be treated first in an emergency room because of abdominal pain resulting from menstrual blood that is blocked. Patients without a uterus may be referred to a specialist like Kolp only after years of hormonal treatment don’t produce a period. Kolp says vaginal agenesis is rarely detected at birth or in childhood. "Unless you’re looking for it—which most people aren’t, and most pediatricians don’t—it’s not usually picked up," she says.

Although most gynecologists might see one case during their entire careers, the Hopkins gynecologist treats several each year, often from out of state. The neovaginoplasty she performs uses skin grafts taken from the buttock. After making an incision where the vagina would normally develop, the gynecologist inserts the grafts to create the canal. A balloon-like device is then put into place for seven days to keep the newly formed vagina open while it heals.

“Girls who are 13 or 14 are shocked to find out they don’t have a vagina, and even more stunned if they learn they don’t have a uterus.” — reproductive endocrinologist Lisa Kolp

When the patient is discharged, she must use a tampon-shaped vaginal dilator to maintain the opening, initially removing, cleaning, and replacing it several times a day. During this phase of healing, Kolp sees her patients frequently, closely monitoring their progress.

Because of the amount of self-care required with this procedure, the gynecologist tries to delay such surgery until patients become sexually active in their late teens or early 20s. Intercourse should eventually be able to maintain the new vagina. Kolp is also working on a device to facilitate the early stages of vaginal construction. With the help of a Hopkins biomedical engineer, she is developing a soft, hollow device that can be inserted after the skin graft heals and safely left in the new vagina for months at a time.

Such a stent would be particularly beneficial for some of her youngest patients, often referred via the emergency room. One of them, a 12-year-old from another state, was MedEvaced to Hopkins several years ago after another physician mistakenly attributed the blockage of her menstrual blood to an imperforate hymen. When the error was discovered during surgery, the patient was sent to Kolp.

"We did the procedure at an earlier age than I would have liked—at the beginning the girl was so scared that she wouldn’t let us touch her or remove her Foley catheter—but we went ahead because her mom and aunts are nurses, and that gave her a skilled support system for afterwards," Kolp says. "Now she has a functional vagina and is having normal periods." Linell Smith

Taming Stubborn Sinuses

New hope for those who suffer from chronic sinus infections.

Andrew Lane says some cases of chronic sinusitis demand a tailored response. Photo by Keith Weller

Imagine your last sinus infection. Now, imagine it lasting for months, even years.

That’s a reality faced daily by patients with chronic sinusitis, who may endure years of blocked breathing, congestion, nasal drainage and a myriad of other symptoms that typically accompany sinus infections. For a subset of patients, antibiotics, surgeries, decongestants, and steroids provide temporary relief, but ultimately the condition returns full-force.

"We are so successful in treating the majority of patients with sinusitis that it is difficult to understand why some patients don’t respond to therapy," says Andrew Lane, director of the Johns Hopkins Sinus Center. "Their noses just stay in this chronic inflammatory state at all times. The million dollar question is, why does that happen?"

It’s a question—along with how to treat and cure patients who suffer from chronic sinusitis—that Lane hopes to answer by drawing on the many resources available in the Sinus Center. "Our clinic tends to draw people who’ve failed medical therapy elsewhere, and so they’re referred here for the specialized care we can provide," he explains.

While sinusitis is common, unrelenting chronic sinusitis isn’t, Lane says. Most people, in fact, do get better with the right treatment. But the ones who don’t might endure scores of medications and surgeries—and even lose their sense of smell—before anything ever improves, if it ever does.

Lane’s goal: to determine what sets patients with chronic sinusitis apart and what remedies prove most valuable. His recent work has focused on the nose’s epithelium.

To best treat these complex patients, Lane believes it’s important to know what causes their condition in the first place. And to that end, Lane studies cells and sinus tissue obtained from patients with chronic sinusitis, and he has also developed mouse models that mimic aspects of the sinus disease human patients suffer.

His goal is to determine what sets patients with chronic sinusitis apart and what remedies prove most valuable. Recent work in his laboratory has focused on the inner lining of the nose, called the epithelium, finding that it may be failing to do its job in blocking germs that cause infection.

Lane estimates that three-quarters of his practice is made up of people with chronic sinusitis. Many have a decreased sense of smell, a problem that is challenging to research or treat because the area of the nose responsible for the ability to smell is difficult to access.

What physicians do know is that inflammation of the nasal passages—one of Lane’s primary research targets—is a defining characteristic of chronic sinusitis. In the nose, he explains, the neurons that recognize odors regularly die off and are replaced when exposed to trauma, including inflammation. In most people, those odor-detecting neurons are regenerated as the epithelium works to fight off disease.

But in chronic sinusitis patients, those processes go awry, and the sense of smell remains decreased or absent as the sinus inflammation persists. Lane hopes his mouse models can contribute to a better understanding of why some patients cannot seem to fight off their illness and keep it off.

Until then, chronic sinusitis patients must rely on the right combination of drugs, surgeries, and medical management.

"Sometimes we can help people with just the right antibiotic," Lane says. "Others need more intensive and prolonged medical treatment or revision endoscopic sinus surgery. Even those referred to us for very recalcitrant chronic sinusitis do experience significant improvement in their symptoms and overall quality of life." Lauren Manfuso