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‹‹‹ Contents page for this issue     |     Winter 2011

Physicians, veterinarians partner to help people, horses to breathe easy

By Susan A. Steeves

The laughing young girl kicking the beach ball wouldn’t seem to have much in common with the middle-aged horse languidly munching grass in the pasture. But they both suffer from inflamed and obstructed airways, known in people as asthma and in horses as heaves and inflammatory airway disease.

“What people with asthma and horses with breathing disorders share is the hope of a better future...”

They are part of an unlikely grouping — a children’s doctor, a veterinarian, the 8-year-old girl, and the 20-year-old horse. It’s the type of relationship that will drive collaborations slated to be the hallmark of the new Virginia Tech Carilion School of Medicine and Research Institute.

Breathing disorders that affect both humans and equines are serious. Approximately 23.5 million asthmatics live in the United States and, in some U.S. regions, as much as half the horse population is afflicted by one of the breathing disorders.

The doctor and the 8-year-old girl

Andy Muelenaer, a Virginia Tech Carilion School of Medicine pediatric pulmonologist, was steered toward his career when he was a Virginia Tech biology undergraduate working on one of the first membrane oxygenators for infants in a biomedical engineering laboratory. Under the tutelage of Leon Arp, a Virginia Tech engineering professor at the time, Muelenaer did work that morphed into a device to help premature infants receive the oxygen they lack because their lungs are not fully formed. Muelenaer worked with bovines and rabbits to prove the worth of the device. In the process, he earned his master’s degree in zoology and decided to go to medical school to become a neonatologist, a doctor who cares for critically ill premature babies. Eventually, Muelenaer decided he didn’t want to do critical care, but loved the gadgets. “Pulmonology offered the best of both — dealing with respiratory problems and plenty of technology,” he says.

In his role as a clinical doctor and chief of the Section of Pediatric Pulmonology/Allergy at the Carilion Clinic Children’s Hospital in Roanoke, he works with youngsters afflicted with breathing problems, most notably asthma.

“Our number-one goal is to allow a child to participate in normal activity,” Muelenaer says. Eight-year-old Summer Wagner is the embodiment of successful treatment of asthma as she runs, jumps, kicks a ball, and hits golf balls, all the while laughing. She was born with asthma. So was her 12-year-old brother Luke. They are part of a three-day summer camp for children with asthma — Catch UR Breath Camp, sponsored by the Carilion Clinic Children’s Hospital and several other medical institutions and businesses.

“Sometimes dust or heat, the weather, make my asthma start,” explains Summer, who says one of her favorite things is doing hula hoop. “I take my inhaler before I do activities.”

Asthma is a chronic disease that can be triggered when something, such as pollen, cat or dog dander, dust, or exercise, sets off an immune response causing the bronchial tubes to become inflamed and constricted. Mucus in these airways thickens and builds up and the muscles around the airways tighten. The signs are coughing, wheezing, a tight chest, and shortness of breath.

Summer and Luke have come to the camp for the past three years. This year Luke is over the age to be a camper but he did so well in previous years that he was asked to be a junior counselor at the camp.

Aside from all his academic and clinical knowledge, Muelenaer can relate to the youngsters who come to the camp and the clinic; he has exercise-triggered asthma and one of his children also has asthma. So, he knows how important it is to diagnose the type of asthma children have and put them on the right treatments.

Asthma can be of four levels: intermittent (generally exercise-induced), mild persistent, moderate persistent, and severe.

About 10% of Olympic athletes are asthmatic

Using state-of-the-art equipment, Muelenaer and his respiratory therapists evaluate children who haven’t had their breathing problems diagnosed and also see youngsters who have been coming to the clinic for years. Some of his patients have gone on to stellar careers in college and professional sports and even competed in the Olympic trials. About 10 percent of Olympic athletes are asthmatic, Muelenaer says.

“Education is as important as diagnosis and treatment,” Muelenaer emphasizes. The clinic team educates parents and youngsters when they come in for evaluation or a checkup; education also is one of the most important aspects of Catch UR Breath Camp. The youngsters learn more about what asthma is, how to manage it, and how important it is to follow the management program they’ve been given by their doctor.

“Once we established treatment protocols in the mid-90s, admissions to the hospital for asthma went way down,” Muelenaer says. “We got smarter about how we treated asthma, and new medications also made a difference.” Despite improvement in treatment and management of the disease, the most recent statistics from the Centers for Disease Control and Prevention (CDC) are that asthma accounts for 1.1 million hospital non-emergency outpatient visits, 1.6 million emergency department visits, and 440,000 hospitalizations in the United States each year. Approximately 4,000 people die annually.

Most asthma begins at birth or in childhood with about 9.5 percent of American children currently diagnosed with the disease — about 7 million, according to the CDC. But the disorder also can develop and/or worsen in adulthood.

The veterinarian and the 20-year-old horse

Although asthma can be treated so that most people can do the activities they love, why asthma happens is unknown, and there is no cure. That’s where the veterinarian and the 20-year-old horse become part of the picture.

Breathing disorders that affect both humans and equines are serious. Approximately 23.5 million asthmatics live in the United States and, in some U.S. regions, as much as half the horse population is afflicted by one of the breathing disorders.

Immune systems in horses and people react to certain triggers that cause airway inflammation and tightening of the associated muscles. Some of the triggers are even the same — dust, debris from mites, weather. But why the immune system reacts the way it does in some people and some horses is unknown. Apparently some genetic factors, combined with exposure to certain environmental factors, result in human asthma and equine inflammatory airway disease and heaves, also called recurrent airway obstruction. Virginia Buechner-Maxwell is investigating what causes the diseases and how to prevent long-term damage from the diseases and the treatments. The goal is better treatments or cures.

“Horses are superb models for studying airway diseases because they develop these illnesses spontaneously, like humans,” explains Buechner-Maxwell, a professor of large animal internal medicine in the Virginia-Maryland Regional College of Veterinary Medicine at Virginia Tech. “They also are the only animals besides people that experience chronic changes of the disease as they age.”

Buechner-Maxwell first learned about the human and the equine forms of breathing disorders when she was very young. Her mother had severe asthma and her first horse was heavey. But her interest in the science was sparked when she was studying for a master’s degree at the University of Pennsylvania and she attended seminars given by their immunology group, which was investigating regulation of the immune response.

“As my understanding of the immune system grew,” she recalls, “I became specifically interested in understanding the events that direct and regulate the immune response because it seems to me that a responsive, well-regulated immune system is critical to good health.”

Asthma and heaves often are the immune system’s response to an allergy, especially to airborne particles. “Allergies in general are a good example of what happens when the immune response is disproportionately intense relative to the inciting cause,” says Buechner-Maxwell.

She is studying both the reasons for the inflammation of the airways and the changes associated with it, how the treatments affect the immune response, and the long-term disease/treatment ramifications.

Heaves in horses is much like asthma in adult humans, especially older people, because they may have worsening disease and long-term lung damage from the disease. Inflammatory airway disease in horses is more like pediatric asthma. In either case, horses and people can be treated the same ways — by keeping them away from the triggers as much as possible and taking some of the same drugs. Horses have even been fitted with surgical mask-type devices so that they can inhale the medication just like people.

Inhaled corticosteroids to minimize inflammation and bronchodilators to open constricted airways are the standard medication now for long-term control of asthma to relieve inflammation. One bronchodilator that is used is albuterol, a beta2–agonist that provides fast-acting relief of airway constriction and often is taken through an inhaler before participating in sports. New research in human medicine suggests that this medication also may influence the nature of the body’s inflammatory response associated with asthma, says Buechner-Maxwell.

She is studying the receptor that binds with beta2–agonists to determine whether these drugs affect inflammatory response in heavey horses as well. Specifically, she is investigating if albuterol affects the types of cytokines that immune cells produce after exposure to an allergen or irritant. Cytokines are small proteins that signal cells to react in different ways. In the case of asthma or heaves, the cytokines produced by immune cells following allergen exposure differ from those that normal people and horses synthesize. Ultimately, these cytokines signal events that result in airway inflammation experienced by affected horses and humans.

The kind of scientific investigation Buechner-Maxwell does is called translational research because the information obtained from studying heavey horses is analogous to what human asthmatics experience. Since horses with heaves or inflammatory lung disease develop the disease spontaneously, the species is a more comparable model with humans than a mouse, a rat, or some other organism engineered to simulate suffering from asthma-like disease.

Horse use as a model for asthma is also important because cell samples can be taken for testing of the immune response without harming the horse. In addition, horses age faster than humans so results of immune responses, drug effects, and long-term disease progression can be studied faster than in human patients. This is an especially important factor when one of the research goals is to better understand chronic lung and bronchial tube changes that occur in people and animals with life-long airway disease.

The research on cytokine expression is ongoing by Buechner-Maxwell and her research team. Currently, they know that some of the signaling that stimulates cytokine response is different in heavey horses’ lymphocytes, a type of immune cell, when compared to the lymphocytes from a horse not plagued by the disease.

“My hope is that by better understanding the events that lead to the ‘inappropriate’ response of the immune system in diseases like heaves and asthma, more can be learned about what promotes and maintains the normal immune response,” Buechner-Maxwell says.

While she works on the disease from both the practical equine side and the molecular research side, Muelenaer has collaborations back where his interest first peaked — Virginia Tech’s mechanical and biomedical engineering departments.

“We currently have five projects related to pediatrics: a pediatric electronic device for emergency resuscitation, an automated oxygen delivery control system, a tracheostomy airflow sensor, a wireless sensor for monitoring and predicting cerebral palsy in infants, and a monitoring system for preterm infants when they’re being transported to medical facilities,” Muelenaer says.

What people with asthma and horses with breathing disorders share is the hope of a better future, thanks to research and collaboration by physicians and veterinarians.

 

Andy Muelenaer, pediatric pulmonologist, talks to Jason Booker and his son, Jonathan, 3, about dealing with childhood asthma. Photo by Kelsey Kradel.

An inhalation mask allows veterinarian Virginia Buechner-Maxwell to administer medicine to 20-year-old mare Jangles, a sufferer of heaves, the equine version of asthma. Photo by John McCormick.

Photo by John McCormick.

Summer Wagner throws horseshoes as part of a three-day summer camp for children with asthma. Photo by Jim Stroup.

Dashaun Grogan runs in a team relay game as part of a three-day summer camp for children with asthma. Photo by Jim Stroup.

Andy Muelenaer, pediatric pulmonologist, sits with Christian Moran, 10, during his asthma treatment at the Pediatric Pulmonary Clinic at Carilion Clinic Children's Hospital. Photo by Kelsey Kradel.

Luke Wagner and an unidentified camper play a ring-toss game as part of a three-day summer camp for children with asthma. Photo by Jim Stroup.

Connor Johnson kicks a beach ball as part of a three-day summer camp for children with asthma. Photo by Jim Stroup.

Sponsors of Catch UR Breath Camp are the Greater Roanoke Valley Asthma & Air Quality Coalition, Carilion Clinic Children’s Hospital, Lewis-Gale Medical Center, Virginia Premier Health Plans, Advance Home Care, Apria Healthcare, Jefferson College of Health Sciences, Merck, Monaghan, Sepracor, and Subway.