A recent study from Pitt researchers found that asthma subtypes in children will soon be diagnosable by a quick swab of the nose.
A team of Pitt researchers found that instead of diagnosing asthma subtypes using a relatively invasive procedure called bronchoscopy, clinicians can use a nasal swab test capable of returning the same results.
Because they are often underrepresented in asthma studies, even though they are more susceptible to asthma, the Pitt research team focused on Black and Puerto Rican children, which can contribute to a fuller understanding of the causes of asthma among minorities.
The study’s primary investigator, Dr. Juan Celedón, found that the new nasal swab test eliminates the need for a bronchoscopy, in which a tube is inserted into the nose or mouth and reaches down into the lungs.
“[Subtypes] had been looked at in bronchial epithelium, but nobody had ever looked at them in nasal epithelium,” Celedón said. “This approach is non-invasive, safe and practical to do at a large scale, unlike bronchoscopy.”
Celedón, a Pitt medical school professor of pediatrics and medicine and the chief of pediatric pulmonary medicine at UPMC Children’s Hospital, said his study refuted the common assumption that T2-high, characterized by inflammation of the airways by infection-fighting cells called eosinophils, is the most common type of asthma. The researchers found that T2-high only accounted for about a quarter of the children studied.
“For many years, T2-high asthma was thought to be the most common type of asthma in youth because it was equated with atopy or being sensitized to an allergy,” Celedón said. “We were able to show that T2-high asthma is in fact less common than the other two endotypes called T17-high and T2-low, T17-low.”
T17-high asthma is characterized by high levels of infection-fighting cells called neutrophils in the nasal airways, and the T17-low, T2-low (low-low) type has neither infection-fighting cell overrepresented in airways.
Kristina Gaietto, an instructor of pediatrics at Pitt’s School of Medicine and a pediatric pulmonologist at UPMC Children’s Hospital, is a member of Celedón’s research team who helped with data analysis on gene expression and provided a clinical perspective of how the study relates to children with asthma.
“The cool thing about this study is that by just scraping the inside of a person’s nose and looking at their gene expression, we’re able to categorize them into these subtypes,” Gaietto said.
After the nose is swabbed, the tissue is sent out for RNA sequencing and sent back to the research team.
Molin Yue, a fifth-year biostatistics doctoral candidate, is a researcher in Celedón’s lab who, collaborating with Gaietto, helped in processing the sequenced data and translating it into transcriptome expression data.
“The data presented in something similar to ‘ATCG,’ like what we learn in the textbooks,” Yue said. “We don’t focus on sequence, but rather we focus on gene expression.”
The study used cohorts of predominantly Black and Puerto Rican children because they have higher rates of asthma, which may be due to exposure to higher levels of air pollutants, tobacco smoke in the home, violence, having less access to fruits and vegetables and having higher rates of obesity. Dr. Celedón said redlining and disparities in healthcare should be considered when analyzing the higher rates of asthma among minorities.
“Almost 100 years later, three generations later, they are still living in areas of high-level pollution, so redlining has a pretty prolonged and detrimental effect,” Celedón said. “Also, their access to adequate healthcare is lower than for whites.”
Gaietto, who has an interest in the psychosocial factors of asthma and has conducted previous research with Dr. Celedón on violence-related distress, also noted the higher rates of asthma in minorities.
“Asthma is not an equal opportunity offender,” Gaietto said. “It disproportionately affects individuals who are Black, Puerto Rican, Alaskan Native, Pacific Islander and Native American … They tend to have more severe asthma and they’re more likely to die from asthma.”
In the past, minorities have been abused in medical research studies. This has caused distrust and a lack of participation in research, resulting in less available data on medical conditions that impact these populations at higher rates. Gaietto referenced the Tuskegee Syphilis Study, in which Black men with syphilis were not told about informed consent and were also not treated with penicillin, despite the fact that it was available for treatment.
“It’s sickening how wrong that is, but things like this happened in the not-so-distant past — we’re talking less than 100 years ago,” Gaietto said. “We have to work harder and include a diverse population in studies of persons with asthma so that we can better understand these disparities and discrepancies in asthma incidences and outcomes.”
Current treatment for T2-high asthma includes biologics, or medication, which include commercial drugs like Xolair, Dupixent, Fasenra and Nucala. But for asthmatics who do not fall into the T2-high category, these biologics do not work.
“As a pediatric pulmonologist, I take care of patients with severe asthma, and it’s so frustrating when they don’t respond to T2 biologics,” Gaietto said. “I don’t have a lot else to offer them because there aren’t existing targeted treatments for T17-high asthma.”
In the future, Celedón says he wants to reproduce the study by tracking asthma endotypes and seeing if they change over a person’s lifetime. Dr. Celedón also said he doesn’t anticipate the nasal swab test to take more than five years to get approved by the FDA. Nonetheless, the study has discovered a new pathway for treating asthma.
“In my point of view, I would say this paper started a new branch of asthma analysis,” Yue said.