A new study1 was released recently that has the potential to change how researchers and doctors classify and treat asthma. The study, written by a group of researchers from England, looked at bronchial biopsies of approximately 200 patients, most with active asthma, but also from a sample group of people who have not been diagnosed with asthma. The researchers also looked at about 60 biopsies from a sample group of patients who had uncontrolled, severe asthma. (These biopsies were from tissue that was already in storage, and were used to show that the results of the study could be repeated in a different sample.)
By using dyes that stained certain cells within the tissue, the researchers could see changes that had occurred to the patient’s tissue as a result of their asthma. The researchers also used dye to look at specific genes and how those genes could possibly affect the type of asthma a patient had. The researchers found four groups, each with smaller “micro-clusters” or smaller sub-groups.
Group 1- Individuals in this group did not have asthma or were those with mild to moderate asthma. Those with asthma had not had an asthma exacerbation in the last year. Within this group, there was a micro-cluster of people with a large percentage of mucous-producing glands in their lungs.
Group 2 – Individuals in this group experienced moderate to severe asthma. About 1 in 4 of these patients (23%) were taking oral steroids regularly. The majority of this group showed signs the bottom layer of cells in the bronchial tubes had grown thicker as a result of their asthma (this is known as “reticular basement membrane thickening”2). There were two micro-clusters in group 2. The first were patients who had adult-onset, severe asthma and the second were patients who had early-onset moderate to severe asthma.
Group 3 – Individuals in this group also experienced moderate to severe asthma. About 1 in 4 of these patients (25%) were taking oral steroids regularly. The majority of this group had a high percentage of airway smooth muscle. This muscle is responsible for the tightening that happens in the airway during an asthma exacerbation.3 The micro-cluster within this group had a high percentage of mast cells (a type of white blood cell that contributes to inflammation and allergies) in their samples.
Group 4 – Most of the individuals in this group had moderate to severe asthma and had the most exacerbations in the prior year, but about 1/3 of the people in this group did not have an asthma diagnosis! This group was characterized by the lack of changes in their airway structure that are normally shown in those with severe asthma.
These results confirm that asthma is a complex condition; patients who are in the same asthma group may have different times of onset, physical changes, and may share symptoms with those who don’t have an asthma diagnosis.
What does this mean for someone diagnosed with asthma?
As researchers are able to figure out what group a patient’s asthma falls in and what genes are responsible for asthma, they may be able to customize treatment to meet the needs of one’s specific diagnosis. This also means that researchers can begin to study how to target treatments specifically for the groups of diseases and begin to study medications that work on the cellular and genetic level.
Having targeted treatment is important for reducing side effects of medications, time off work or school due to asthma exacerbations, and reducing long-term changes in the body due to asthma. While these targeted treatments will take time to develop, studies such as this help give researchers clues in where to begin improving asthma medications and treatments.
Airway pathological heterogeneity in asthma: Visualization of disease microclusters using topological data analysis. Siddiqui S., Shikotra A., Richardson M., Doran E., Choy D., Bell A., Austin C.D., (...), Bradding P. (2018) Journal of Allergy and Clinical Immunology
Liesker, J. J., Hacken, N. H. T., Zeinstra-Smith, M., Rutgers, S. R., Postma, D. S., & Timens, W. (2009). Reticular basement membrane in asthma and COPD: Similar thickness, yet different composition. International Journal of Chronic Obstructive Pulmonary Disease, 4, 127–135.
Doeing, D. C., & Solway, J. (2013). Airway smooth muscle in the pathophysiology and treatment of asthma. Journal of Applied Physiology, 114(7), 834–843. http://doi.org/10.1152/japplphysiol.00950.2012