Asthma

Asthma

The elderly man, nearly 80 and bent with age, coughs hard and long. By now, he is hoarse from several days of such attacks. After years of this, I have learned to make sure he gets to the doctor. Another round of antibiotics. Another prayer. Another hope that drugs continue to beat back another infection in lungs severely scarred by asthma and chronic obstructive pulmonary disease. A lifetime of fieldwork on the farm-grain dust, crop chemicals, exhaust from farm machinery and other allergens-takes its toll. I can barely imagine how it feels based on my childhood asthma experiences gasping for breath. But his attitude of mind over lungs makes a difference.

The same optimism appears in the petite woman with sandy-colored hair, dark-framed glasses and an energetic smile. She's never met my father. But her father, once a farmer, possesses that way of viewing the world too, she says. At 50, her father injured his back, making farming impossible. He then attended NDSU to earn a teaching degree and later inspired biology students in the classroom at Sheldon High in southeastern North Dakota. Jane Schuh, assistant professor of microbiology at NDSU, tries to emulate her father's teaching methods. She points out he didn't play favorites as she sat in his class. "I'd always raise my hand and he'd say, 'Yes, Jane, we know you know the answer," smiling as he called upon another student.

While still in high school, things changed with a single diagnosis. Multiple sclerosis.

"That was a turning point," she recalls. As her father's MS progresses over more than two decades, optimism makes a difference. "He is a man with a tremendously positive attitude and a deep faith." Pair that with Schuh's experience with her mother's health issues during Jane's childhood. One result of that environment-a family with a helping gene in its DNA. With 10 kids, there are lots of hands to help. They bunked four to a room in their tiny trailer home. "Lots of kids to play with when you have that many siblings," says Schuh, the second youngest of the crew. She ticks off their professions as adults-doctors, middle school principal, nurses, drug rehab staff, plant manager, marketing manager, academic researcher and a school paraprofessional.

As an undergrad at NDSU, Schuh studied zoology. "People would ask how I went from zoology to microbiology-big animals, little animals," she says, calling it an asset to her research. "Lots of times I've gone back to my zoology roots and think, this doesn't make sense because an organism doesn't waste time and energy making a bunch of stuff that it doesn't need. So why are they making all this protein and how is it being used? Obviously, if they're making it by the bucketloads, it's important for something. We just have to figure out what."

big curiosity = big research
Sometimes science, like a career, takes serendipitous turns. "I didn't get into med school, which was probably a good thing." After completing her doctorate degree in cellular and molecular biology at NDSU, Schuh's postdoctoral work at University of Michigan Medical School occurred in an immunology lab led by a former North Dakotan. Work at the lab focused on asthma research. "There are so many things that we don't know about asthma-number one being what causes it," says Schuh. "We think it's genetically mediated and allergy and environmental factors play a role."

The practical nature of a farm girl from a large family weaves through Schuh's research. "If you're responsibly looking at a research program, for me that means you need to be looking at hypothesis-driven research. You need to have something that's worth funding," she states matter-of-factly. "With asthma, you can ask practical questions. With your research, you can, hopefully, impact the disease or people's therapy or potentially figure out what causes the disease so people don't get it in the first place."

As asthma drags on through a person's lifetime, it may physically remodel and change the airways. "Your airway gets smaller and smaller and it's like breathing through a swizzle stick," explains Schuh. Smooth muscle increases around the outside of the airways, so when they clamp down during an asthma attack, they really clamp down-like a vacuum cleaner sucking air out of a plastic bag.

Healthy lungs are capable of expanding when you need more air or shrinking when you need to cough, for example. But lungs beat up by chronic lung disease don't have that luxury. Bronchial fibrosis can develop. "It's like laying down cement around those airways," notes Schuh. "That cement-like substance around airways limits their ability to expand and constrict. That's what the dysfunction is in a lot of people with chronic lung disease.

Shuh points to staggering statistics. Each day in the U.S., asthma causes 40,000 people to miss work or school. Each day 30,000 people have an asthma attack. There are another 5,000 people who visit the emergency room daily due to asthma. And 11 people die-each day, according to the American Academy of Allergy, Asthma and Immunology.

There's no abatement in sight to the enormous numbers. Asthma rates in children jumped 160 percent from 1980 to 1994, according to the Centers for Disease Control, with a 75 percent increase in the general population during the same period. Then there's the price tag. The Asthma and Allergy Foundation estimates $18 billion in direct health care costs and lost productivity each year.

Schuh particularly notes what some refer to as a childhood asthma epidemic. "That's horrible to think that these little 5-year-olds who have asthma are going to be 50-year-olds who have asthma, that are going to be 75-year-olds who have asthma." The disease doesn't discriminate between urban and rural dwellers. A common thread, though, is whether you can afford health care services and whether you have access to them. "I grew up on a farm. During harvest, planting, almost any time, you had to be there," says Schuh. "There's no way I can see even a well-meaning parent taking their kid 60 miles to the doctor to get treated for wheezing. So these people 50, 60, 70 years later have horrible lungs and have never been diagnosed even as asthmatic."

She says people often mistakenly believe that kids outgrow their asthma. Actually, airways get bigger, making it easier to move air in and out. And people simply get more clever at avoiding triggers like grass pollen or animal dander or mold that induces their asthma. So Schuh and her team are looking for answers. Some people want to build a better mouse trap. Jane Schuh wants to build a better mouse model.

She admits there are good and not so good aspects to using an animal model for asthma research. The animal is given the disease and tracked all the way through. "You can go from the initiation to the maintenance and chronicity of the disease." Variables are controlled. The lungs of a three-inch mouse don't exactly mimic those of a 150 lb. person, but this type of model allows researchers to quickly see the effects of the disease. Symptoms occur in mice within weeks, rather than the decades it takes in humans. "Animal models tell us a huge amount but should be used judiciously and appropriately."

Her asthma research focuses on finding candidate genes or targets for asthma, on what initiates the disease process early and shows up later. In the course of every day, "You're breathing all sorts of junk-dander, molds, pollen, pollution, smoke-that attack the lungs," says Schuh. While most body organs are well-protected as they do their respective jobs each day, lungs are unique. Lungs have one cell thickness between the outside and inside to get air in and out. "Probably our immune system tries to make sense at that interface and deals with it the best way it can. How do we help it deal?"

Schuh's first research funding from the National Institutes of Health went toward developing a novel model for asthma research. Part of the problem, as she views it, is that a lot of mouse models don't use an appropriate allergen. "The leading mouse model for asthma or allergic airway disease as it's called, uses ova albumin. Most humans don't snort chicken eggs," laughs Schuh. Instead, her research model uses the fungus Aspergillus, since fungus is a prevalent asthma trigger.

In a frequently-accepted research model, fungal spores in liquid are injected directly into the trachea, which allows researchers to control exactly how many spores go into every mouse. But the spores are tiny and hydrophobic, so the liquid doesn't penetrate very far into the airways or the itty bitty alveoli of its subjects.

"I thought, let's figure out another way." So Schuh and her research team use a different method-essentially blowing air across fungal spores in a miniature respiratory chamber for mice. They monitor the results. After 35 days, they find fibrosis in the airways and some smooth muscle, which isn't usually there. Even after the initial inflammation from the spores subsides, the airways are changing and remodeling. "We hit them once with these fungal spores. Even after inflammation resolves 35 days later, we see a lung that looks a lot different. What's going on with those lungs?" Schuh is currently submitting the results of this research to several scientific journals.

big research = big discoveries
An early riser from her days on the farm, Schuh awakes at 4 a.m. each day. "I don't get out of bed right away. It's quiet. And I think. Hmmm. IgA-I just read a paper. I wonder what IgA is doing in our model." She later checks the immunoglobulin A antibody in her lab experiments and it's increasing. "IgA in the lungs is shootin' up." Or she thinks about whether a live fungal spore produces the same response as a dead fungal spore. Then she tests it in the lab.

She never thought in a million years she'd be back in North Dakota doing research. But while she was working in Michigan, another graduate student at NDSU, Scott Hoselton, now the technician in her lab, e-mailed her about opportunities at her alma mater. When her former professor and mentor Michael Robinson left NDSU, an immunology position opened up. "I called people I knew here to find out where NDSU was going with research and the answer from everyone was that this was a very exciting time to be at NDSU. There have been pushes in the past to get research going, but there's never been the financial backing that there has been in this era." So in 2004, Schuh declined other tenure track offers, saying NDSU provided her the best place "to do research and teaching like I wanted to do it."

She is also part of a research group led by Mukund Sibi, professor of chemistry at NDSU, who received a $10.5 million grant from the National Institutes of Health-among the largest single grant awards in NDSU's history. The group researches the role of protease or enzymes in a variety of diseases, including asthma.

Schuh appreciates the biomedical research underway with colleagues here in chemistry, microbiology and other fields. "You bring them all together and all of a sudden you've got a critical mass. You have people who on a regular basis get together and talk science and are talking biomedical science." Such interaction is crucial as she learned in her days as a postdoctoral fellow at the University of Michigan Medical School.

By 7 a.m. each morning, everyone was in the office chatting. Someone would mention a drug company had a new product to test for lung function. Someone else would say, "Did you see the scientific paper that was published?" As an early bird, Schuh always participated in the discussions, realizing that's how discoveries begin. "It's not the 8 to 5 and going to the symposia. It's sometimes having a burger with somebody and mentioning that 'I saw this paper, have you read it'?" And she is just as enthusiastic about the rest of her research team heading down the same path. "We do molecular biology, fungal biology, surgery, immunological testing, histology. I tell the Ph.D. students that once they leave this lab, they will have an arsenal of things they can do."

big liver = big heart
Schuh clearly possesses many attributes. Big curiosity, big enthusiasm, big heart and big liver. Liver? In 2007, when one of her brothers-in-law developed liver disease and needed a liver transplant, her large family once again sprang into action. "I was actually one of a number of people in my family willing to donate. I have a brother and sister-in-law who tested but weren't a match." Another brother-in-law was next on the list to donate after Schuh. "That's the gift for being healthy. You get to donate a large chunk your liver," she says, smiling. "I knew, if it were me, someone would do it for me."

She pauses for a moment. "They have three beautiful girls," she says, her voice cracking, as she recalls the decision to help her younger sister and her husband, who is doing well after the transplant. She downplays the enormity of her gift. And in optimistic Jane Schuh fashion, says "It was cool, quite honestly." She found the science of the entire process fascinating. Even after suffering a massive post-transplant reaction to medication, her enthusiasm still isn't dampened. She underwent the eight-hour surgery only nine months after the birth of her own daughter.

It's a bumpy ride on the transplant train. "The first couple weeks, you feel miserable," she recalls. "At four weeks, I felt rough. At five weeks, I felt good." The transplant team pointed out that Schuh has an unusually large liver for her size. She's amazed at how fast the organ regenerates. "Within five weeks, it was completely regenerated. The doctor said, 'How did you know?' I told him, because when I rolled over in bed, everything didn't go phuloop!"

Schuh emphasizes a supportive environment made the process possible. Her husband stays at home with their son and daughter. And her lab staff keeps research on track. "It was very well supported in the department and across campus," says Schuh, pointing out that her department chair had earlier donated a kidney to his brother. The only drawback, she says, was that she couldn't pick up her daughter for a long time after the surgery.

big discoveries = big answers
Three pairs of shoes are lined up in one neat row underneath the floor-to-ceiling bookshelf in Schuh's office. The brown, comfy, sherpa-lined clogs sit cozily next to tan Ugg booths and on the other side, some utilitarian brown, closed-toe loafers rest quietly.

"These are warm," says Schuh, pointing to the boots. The clogs play another role. "Comfortable feet are very important to think when I'm sitting at my computer so I'll be padding around in my slippers,"she says. The practical closed-toe shoes are the safety-conscious choice for working in the lab in the summer.

A cartoon from a local newspaper hangs in her office, autographed by her colleagues in the department. It shows a lab technician from the National Institutes of Health in his white coat, peering through a microscope with the letters NDSU in a petri dish. In the balloon above his head, the technician tells Uncle Sam who's standing behind him, "We've found someone capable of making creative discoveries in the treatment of asthma and cancer."

My dad, me, my daughter, my cousins and my cousins' children all have asthma. At family gatherings, you don't need to worry if you forget your rescue inhaler. Some other family member can whip out albuterol quickly if you need it. On behalf of my family's asthma-laden dynasty and countless others like us, we hope Jane Schuh finds big answers.

-- Carol Renner