Increased eosinophil count and fractional exhaled nitric oxide levels have been linked to an increased risk of experiencing a severe asthma attack.
Type 2 inflammatory biomarkers are associated with a 1.4-fold increase in the risk of severe asthma attack, a new systematic review and meta-analysis has found.
Type 2 inflammation is a common yet preventable inflammatory response that occurs in asthma. Despite this, little is known about the extent to which the biomarkers associated with type 2 inflammation affect the risk of asthma attacks. Now, a new study, published in The Lancet Respiratory Medicine, provides some answers on the matter.
Researchers pooled individual-level data from over 6500 asthma patients enrolled in 22 previous clinical trials in an attempt to quantify how accurately baseline sociodemographic characteristics and type 2 inflammatory biomarkers – specifically blood eosinophil count and fractional exhaled nitric oxide (FeNO) – could predict asthma attacks.
While patients had to be at least 12 years of age to be included in the current meta-analysis, the final cohort were much older (median age 50). Patients were predominantly female (64%) and most come from Europe or North America (38% and 32%, respectively). Four in every five patients had experienced a severe asthma exacerbation in the previous 12 months.
After accounting for relevant factors in their analyses, each 10-fold increase in baseline blood eosinophil count and FeNO were associated with a 1.4-fold increase in the risk of a severe asthma attack (rate ratio of 1.48 for eosinophil count and 1.44 for FeNO).
Patients at the 75th percentile for baseline blood eosinophil count (0.42 x 109 cells/L) had a 1.2-fold increase in the risk of severe asthma attack compared to patients at the 25th percentile (0.14 x 109 cells/L). Similarly, patients at the 75th percentile for baseline FeNO (42 parts per billion) had a 1.1-fold increase in the risk of having an attack compared to the 25th percentile (14 ppb).
“The incremental relative risk associated with these biomarkers and key clinical prognostic factors implies that the absolute risk due to type 2 inflammation is greater in patients with additional clinical prognostic factors,” the researchers suggested.
“Such substantial changes in these measurements reflect those that can occur with the initiation or discontinuation of an anti-inflammatory treatment.”
The researchers said a combination of blood eosinophils and FeNO had the potential to be a more useful predictor of risk than either measure alone because each biomarker reflected a different aspect of the type 2 immune response seen in asthma.
“Blood eosinophil counts reflect circulating IL-5 and the systemic pool of available effector cells, whereas FeNO is an IL-13-mediated biomarker also reflecting type 2 cytokine, chemokine and alarmin signalling in the airway compartment,” they wrote.
“Accordingly, elevations of both of these biomarkers are likely to be associated with migration of eosinophils to the bronchi and the development of airway pathology associated with asthma attacks, including abnormal mucus production, airway wall thickening and increased bronchial motor tone.”
Related
Several other factors were associated with an increased risk of asthma attacks, including experiencing an attack in the previous year (RR 1.94 compared to patients who did not experience an attack), being female (RR 1.24) and chronic rhinosinusitis without nasal polyps (RR 1.20).
However, bronchodilator reversibility was associated with a lower rate of severe asthma attacks (RR 0.93). This finding was somewhat surprising to the researchers, as this particular measure is commonly used as a diagnostic tool and inclusion criterion for asthma-related clinical trials.
“Overall, these findings have important implications for clinical practice as they highlight the shortcomings of relying on symptoms, lung function and bronchodilator reversibility to identify patients at high risk and make individualised treatment decisions,” the researchers concluded.
“These findings underscore the importance of comprehensive risk stratification of people with asthma.”
