Fighting for breath
Dr. Lisa Cameron hopes to solve some of the genetic mysteries behind asthma and allergies.
Story by Tara Narwani/Illustration by Veer
Most of us take our breathing for granted. We expect each breath to be easy. But people with asthma face a disease that threatens their ability to breathe. Inhaling the wrong substance can trigger an asthma attack. If they have allergies as well, they may make the asthma symptoms worse.
What happens in an allergic asthma attack? When the body's immune system detects a foreign substance (the allergen) and sounds the alarm, the muscles surrounding the airways tighten and go into spasm. The result: shortness of breath, coughing, and a characteristic wheezing sound as the person struggles to breathe. To fight the inhaled invader cells, immune cells in the airways release histamine and other inflammatory chemicals, which start to inflame the airway walls. This is the first phase of the attack; it may or may not be followed by a second phase several hours later.
The second phase generally lasts longer than the first, and symptoms can be even stronger. In addition to airway muscle constriction, the airway tissue becomes inflamed and swollen, making the air passages even narrower. The lining of the airways releases extra mucus—which takes up even more of the precious air space—in an attempt to envelop the invaders and carry them out of the body. The most severe attacks can lead to suffocation.
Some cases of allergic asthma can be managed by avoiding the allergen—the specific substance that induces the condition. Most, however, require medication. Because each individual reacts differently to asthma, and current asthma medications vary in their effectiveness on particular symptoms, there is always the need for new treatments. "Asthma is characterized by a range of symptoms that arise as a consequence of both the genetic and environmental circumstances of each patient," explains AHFMR Scholar Dr. Lisa Cameron. In the future, she believes, treatments will be tailored to the unique circumstances of each patient.
Dr. Cameron investigates the role of allergies in the development of asthma. She wants to determine what controls a particular gene that plays a role in the allergic response in people who have asthma. The immune response in people with allergies is, by definition, abnormal; that is, they react quite severely when they inhale certain substances that would elicit very little or no response at all in the average person. But if they also have asthma, their allergic reaction will exacerbate their asthma symptoms.
The early phase of an asthma attack is associated with acute, immediate asthma symptoms. It may or may not be followed by a second phase. This later phase contributes to the chronic symptoms of asthma. "The late-phase response creates a perpetual cycle that continues to release chemicals that restrict breathing," she explains. It is this phase that is of particular interest to Dr. Cameron; her work focuses on a specific component of this cycle and how it is regulated.
A type of immune cell called a Th2 lymphocyte plays a key role in the late-phase allergic response. Each Th2 cell has a receptor protein called CRTh2 on its surface. Allergy conditions alert this protein to produce certain chemical messengers. The messengers, in turn, recruit more immune cells, which increases the inflammatory response. This can become a runaway process. The resulting inflammation of the airways in asthmatic lungs becomes chronic and can cause permanent changes to lung tissue.
Because CRTh2 is involved in the late-phase allergic response, Dr. Cameron is investigating the factors controlling the activation of the gene that produces this protein. She and her colleagues have discovered that changes in the genetic sequence for CRTh2 can influence the development of allergies in people with asthma. Now she is conducting tests to see how these changes cause increased activation of the gene, which in turn can increase the inflammatory response.
The fundamental question is whether changes in CRTh2 gene activation can change the allergic response, and ultimately reduce the severity of an individual's asthma symptoms, or even lessen that individual's propensity to develop the disease in the first place. If so, this knowledge could lead to a range of new asthma medications targeted at individuals with specific genetic variations.
Dr. Cameron's passion for her work is clear when she talks about its possible impact. "Given the complexity of the disease, the future of asthma treatment is undoubtedly personalized medicine. This frontier can only be opened up, however, with continued progress in basic research. This dual goal-to understand the biology of human disease and to improve asthma treatment and the life of these patients-is what makes the work exciting."