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Elevated Serum cAMP Findings May Allow Asthma Diagnosis by Blood Test

Key Takeaways

  • Elevated cAMP levels in asthma patients' blood may enable diagnosis and severity assessment via a blood test.
  • A transporter protein, not phosphodiesterase, facilitates cAMP leakage into the bloodstream.
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Current asthma diagnosis requires specialized breathing tests that can be challenging for young children.

 Reynold Panettieri, MD, vice chancellor for Translational Medicine and Science at Rutgers University,q

Reynold Panettieri, MD

Credit: Rutgers University

New research has found that cyclic adenosine monophosphate (cAMP) is highly elevated in the blood of people with asthma, enabling diagnosis and possibly severity determination with a simple blood test.1

"What we discovered is a specific transporter, a protein on the membrane of airway smooth muscle cells, allows cAMP to leak into the blood," senior investigator Reynold Panettieri, MD, vice chancellor for Translational Medicine and Science at Rutgers University, said in a statement.2 "For decades, we believed that an enzyme called phosphodiesterase was the critical factor in decreasing cAMP. We now refute that and say this transporter simply leaks it out."

Panettieri and colleagues analyzed blood samples from 87 patients with asthma, 39 of which had severe asthma, and 273 participants without asthma. They found that cAMP levels were consistently higher in the blood of asthma patients by up to 1000 times and correlated with disease severity. The findings may offer a new tool for monitoring patient conditions.1

"It's really difficult to do lung function tests in kids under the age of 5," Panettieri said.2 "However, our data suggests that if you just did a pinprick, maybe you could diagnose kids who can’t access or do lung function tests."

Looking at serum cAMP levels between severity groups, the investigators found no significant difference between severe asthma and nonsevere asthma serum cAMP levels but each asthma group showed significantly higher cAMP levels (adjusted P < .00001) than the non-asthma group. They did not find any significant associations between serum cAMP levels and clinical traits of asthma, however, serum cAMP levels did arithmetically increase with the number of inhaled corticosteroids puffs and controllers used and, in the nonsevere asthma group, with the increases of post-bronchodilator lung function.1

"If you look at city dwellers, about 1 in 15 people has asthma," Panettieri added.2 "It’s incredibly common — the number one reason kids go to the emergency room."

Panettieri and colleagues are working to develop a point-of-care test for doctors' offices after initial attempts at a simple lateral flow device were not sensitive enough.

"We would anticipate maybe in the next 6 months, we'll have nailed the fidelity of it, get it into our intellectual property and patent the test itself, and then in a year to 2, it could become available," Panettieri said.2

The investigators concluded by noting that further studies are needed to explore associations between serum cAMP levels and bronchodilator or treatment responses by asthma severity; ABCC1 expression and activity in health and disease, including specific cell types of origin; and whether these physiological outcomes and clinical phenotypes are affected by variations in ABCC1 genotypes in a large cohort of patients with and without asthma.1

"Every disease we study or treat is not one disease," Panettieri added.2 "There are different aspects and attributes within a disease entity."

REFERENCES
  1. An SS, Cao G, Ahn K, et al. Serum cAMP levels are increased in patients with asthma. J. Clin. Investig. Published online January 7, 2025. doi: 10.1172/JCI186937
  2. Scientists Discover Potential Blood Test for Asthma Diagnosis and Severity. News release. Rutgers University. January 15, 2025. https://www.rutgers.edu/news/scientists-discover-potential-blood-test-asthma-diagnosis-and-severity
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