Blood test uses cyclic adenosine monophosphate to diagnose asthma
Key takeaways:
- Patients are prone to airway contraction when cells lose cyclic adenosine monophosphate.
- Patients with asthma had higher average serum cAMP levels than patients who did not have asthma.
Blood tests for cyclic adenosine monophosphate may be a simple and useful option for diagnosing asthma and determining its severity, according to a study published in The Journal of Clinical Investigation.
Alternatives are beneficial because “multiple challenges exist” in asthma diagnosis, Reynold A. Panettieri Jr., MD, vice chancellor for translational medicine at Rutgers University, told Healio.
Chest tightness, cough and wheeze, which Panettieri called the “sentinel symptoms” of asthma, are very common and could be associated with a variety of diseases. Also, Panettieri said, “asthma can occur at any age,” from infancy through old age.
“The other challenge in making the diagnosis is that it comes and goes. It waxes and wanes,” he said. “When a patient isn’t particularly symptomatic, some of their breathing tests could be perfectly normal.”
Or, he said, primary care providers and other physicians who treat most patients do not have access to tests such as FEV1, forced vital capacity or fractional exhaled nitric oxide, requiring them to refer patients to specialists.
“Those are the real challenges in today’s platforms,” he said.
However, the researchers discovered that patients with asthma have significantly higher levels of cyclic adenosine monophosphate (cAMP) in their blood than patients who do not have asthma, sometimes by a factor of up to a thousand.
“All cells generate cAMP,” Panettieri said. “When cAMP goes up in inflammatory cells or in the smooth muscle, inflammation goes down and the muscle relaxes.”
But when cAMP leaks from cells, he continued, smooth muscle contracts and causes chest tightness, cough or wheeze. The researchers hypothesized that higher levels of cAMP in blood would indicate greater leakage and the presence and severity of asthma.
“What we’ve now come up with in this study is the first time that we’ve been able to characterize the severity of the disease and the presence of asthma by a simple blood test that could be done potentially at any LabCorp or elsewhere,” Panettieri said.
The retrospective study used serum samples from 87 adults with asthma (69% women; 69% white), including 39 patients diagnosed with severe asthma (67% women; 64% white), from the Severe Asthma Research Program-3 biobank.
It also used serum samples from 273 adults who did not have any known history of asthma (65% women; 49% white) in the Rutgers Corona Cohort study as healthy controls.
The cAMP levels ranged from 0.291 pmol to 563.9 pmol in the asthma group and from 0 pmol to 27.72 pmol in the control group, which the researchers called markedly smaller. Medians included 6.22 pmol for the asthma group and 0.52 pmol in the control group, which the researchers called significantly lower.
Linear regression models using age and sex as covariates yielded median cAMP levels of 4.547 pmol for patients with nonsevere asthma and 8.625 pmol for patients with severe asthma.
“It didn’t reach statistical significance because it was a relatively small sample size, but the directionality in the arithmetic means were heading in a direction that would suggest higher levels would be associated with worse asthma,” Panettieri said. “We have to obviously confirm that in a larger study.”
The severe asthma group and nonsevere asthma group both had significantly higher cAMP levels compared with the control group (P < .00001) as well.
However, the researchers said, there were no significant differences in cAMP levels between patients with eosinophilic asthma, defined as 300 cells/µL or higher, or neutrophilic asthma, defined as 4,000 cells/µL.
“But again, the sample size was small,” Panettieri said. “My hope is that we will see some difference, because now we have something to follow patients when their asthma comes under control.”
Also, there were no significant differences based on indicators of poor asthma control, defined by Asthma Control Test scores and the use of inhaled corticosteroids, oral steroids and controllers.
There were not any significant differences in cAMP with maximum FEV1 reversibility with albuterol either, the researchers continued, although levels arithmetically increased with increases in inhaled corticosteroid puffs and controllers used.
Additionally, cAMP arithmetically increased with increases in post-bronchodilator lung function in patients with nonsevere asthma, the researchers said.
“All the bronchodilators that we use increase cAMP in the cells,” Panettieri said. “If you have more severe airflow obstruction, maybe it’s in part because the smooth muscle cells leak more cAMP from the cell and can’t retain cAMP.”
Although the sample size was small, Panettieri said, cAMP appeared somewhat independent of whether a patient used a bronchodilator.
“It’s not simply the fact that these people are on medicines that increase cAMP, and that’s why you get a lot in the blood,” he said. “That didn’t follow.”
Based on these findings, the researchers called for further studies investigating associations between serum cAMP levels with bronchodilator or treatment responses based on asthma severity.
Further, the researchers called for studies of ATP-binding cassette subfamily C member 1 (ABCC1) expression and activity in health and disease as well as whether variations in ABCC1 genotypes affect these physiological outcomes and clinical phenotypes among a large cohort including patients who have and who do not have asthma.
“This was a retrospective study,” Panettieri said. “We’re planning to prospectively test our findings. See patients in the office, measure their levels and then predict whether they have asthma or whether the severity of their asthma is worse based on cAMP levels.”
These findings would guide the creation of a point-of-care test, the researchers said, which would be useful for pediatric patients who could not perform the breathing tests required by other diagnostic measures. It also would be useful for general practitioners who do not have access to those tests or equipment.
“We could use a simple finger prick and give you a high, medium or low reading that would inform the provider that this patient may have asthma and characterize their severity,” Panettieri said.
Reference:
- Scientists discover potential blood test for asthma diagnosis and severity. https://www.rutgers.edu/news/scientists-discover-potential-blood-test-asthma-diagnosis-and-severity. Published Jan. 15, 2025. Accessed Jan. 21, 2025.
For more information:
Reynold A. Panettieri Jr., MD, can be reached at rp856@rbhs.rutgers.edu.