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  1. Good Science Digest

  2. Jul 18, 2018

Asthma Research for the 21st Century

The first in a series of three posts examining asthma research and testing methods, this post provides some general information about asthma research and testing methods and how they can be improved.

Asthma: Chances are either you or someone you know is affected by it. But how do researchers study asthma and how can we do a better job?

Asthma is one of the leading chronic health conditions in the United States. More than 26 million people are known to have asthma nationwide, and the prevalence is rising. Each year, asthma in the United States costs approximately $56 billion in medical costs, lost school and work days, and early deaths. Asthma is attributed to approximately 500,000 hospitalizations and over 3,500 deaths annually, yet there is no cure.

Asthma is a chronic lung disease that inflames and narrows the bronchial tubes—or airways—that carry air into and out of the lungs. A combination of poorly understood genetic and environmental factors contribute to any one person’s asthma diagnosis. But in most people, asthma causes recurring periods of wheezing, chest tightness, shortness of breath, and coughing. People who suffer from asthma have inflamed airways that can strongly react to inhaled or ingested substances such as environmental allergens, chemicals, sulfites in foods and drinks, medications, air pollution, and other irritants. When the bronchial tubes react, the muscles around them tighten and the cells inside the airways produce excess mucus, which further restricts airflow. Asthma symptoms can range from mild to severe and may cause hospitalizations and even death.

Over the past several decades, research has identified two types of prescribed asthma therapeutics, which are classified as either controllers or relievers. Controllers are long-term control medicines that help reduce airway inflammation and prevent asthma symptoms. Relievers, or “rescue” medicines, relieve asthma symptoms on the onset of a flare-up. Despite decades of research, neither of these types of medications addresses the underlying cause or causes of disease, and significant asthma-related morbidity and excess healthcare use and costs persist. 

Animals have been extensively used in asthma research to examine mechanisms of disease, the activity of gene and cellular pathways, and to develop and test drug therapies. Numerous animal species are used for experiments, including mice, guinea pigs, dogs, cats, sheep, and horses, among others. Unsurprisingly, animals are poor candidates for studying asthma because the anatomy, immune system, and inflammatory responses exhibited by animal lungs differ greatly from those in humans. Animals used to study this condition do not exhibit symptoms similar to human asthma—asthma is a human disease—, so typically the disease has to be artificially introduced in the airways. Animals also have different airway architecture and different breathing behaviors that affect where the inhaled irritant “lands” in the lung and therefore how the organism reacts. Furthermore, the distribution of lung inflammation is different, and many animals become tolerant after repeated allergen exposure. Therefore, key features of human asthma cannot be recreated in animal models.

Researchers can learn much more about the complexity and diversity of asthma from human-relevant research rather than animal experiments. Instead of genetically modifying mice or subjecting animals to inhalation chambers or extreme, unnatural sensitizing processes, researchers can focus on promising, human-relevant research methods. For example, since asthma is such a widespread condition, epidemiological studies using human volunteers with asthma can provide key information on likely triggers and responses to drugs.

In recent years, researchers have developed a small airway-on-a-chip that enables analysis of human lung inflammation and drug responses in vitro. This model is a small silicone chip lined with human cells that can simulate human lung inflammatory disorders like asthma. It can be used to detect synergistic effects of asthma triggers and to identify biomarkers of disease exacerbation as well as responses to anti-inflammatory compounds.

Genetics are thought to be a significant risk factor in the development of the disease. Many genetic studies are currently taking place in the field of asthma research, such as sampling cell cultures from people with asthma and analyzing them to see which genes are different and how that impacts their potential response to treatment. A person’s environment can impact their genes, which makes genetic asthma research complicated, but gaining a better understanding of the genetic contributors to human asthma will lead to improvements in diagnosis, treatment, and, hopefully, prevention.

Human-based approaches offer a more relevant and personalized way to examine this human disease. After decades of asthma exploration there is sufficient research but insufficient progress. Asthma is a complex disease with a lot of diversity, making sophisticated human-relevant approaches necessary to deepen our knowledge of this universal human health condition. 

Stay tuned for an in-depth discussion of some promising human-cell-based models for research and testing!

References

  1. National Center for Health Statistics: Asthma. Centers for Disease Control and Prevention Web site. https://www.cdc.gov/nchs/fastats/asthma.htm. Published March 31, 2017. Accessed July 5, 2018.
  2. Asthma. National Institutes of Health National Heart, Lung, and Blood Institute Web site. https://www.nhlbi.nih.gov/health-topics/asthma. Accessed July 5, 2018.
  3. Benam KH, Villenave R, Lucchesi C, et al. Small airway-on-a-chip enables analysis of human lung inflammation and drug responses in vitro. Nature Methods. 2016;13:151-157.
  4. Corry DB, Irvin CG. Promise and pitfalls in animal-based asthma research. Immunologic Research. 2006;35:279-294.

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