Biomarkers Could Signal Relapse Risk in Adults With Spontaneous Asthma Remission

Biomarkers may be able to predict which patients with spontaneous asthma remission are at the highest risk of relapse or lung function decline, according to a new study.

The report found bronchial hyperresponsiveness (BHR) and serum inflammatory cytokines are key predictive biomarkers. The results were published in the journal Allergy.

Many people who are diagnosed with asthma as children will see remission as they grow into adulthood, but some of those patients will experience a relapse or a series of relapses and remissions, noted the investigators.

While the long-term effects of asthma on lung function have been widely studied, the investigators said it is less well known whether subclinical inflammation during remission might also impact respiratory outcomes.

“Current management primarily focused on asthma symptoms may miss a subset of ‘at-risk’ individuals in whom routine follow-up with repeat spirometry might be beneficial,” the authors said.

Dharmage and colleagues suspected that systemic and airway inflammation might continue in some adults with spontaneous asthma remission, and that biomarkers of inflammation might be helpful tools in predicting which patients require the closest monitoring.

The investigators used data from the Tasmanian Longitudinal Health Study, a cohort of 8583 children born in Tasmania in the year 1961 who have been evaluated at key time points ever since. Those patients underwent testing for biomarkers of systemic inflammation at age 45, and assessment of BHR and nitric oxide products in exhaled breath condensate (EBC NOx) at age 50. The subsets of patients who had spontaneous asthma remission at ages 45 and 50—466 and 318 patients, respectively—were assessed again at age 53 to see whether biomarker links with outcomes could be identified.

The data revealed a number of key findings. First, the authors stratified patients into 3 groups based on cytokine levels: average, T-helper 2 (Th2)-high, and Th2-low. The 2 outlier groups were found to have notable outcomes. Those participants in the Th2-high group had an accelerated decline in post-bronchodilator measures of forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) scores (MD −0.18% per-year; 95% CI, −0.33, −0.02).

Patients in the Th2-low group had an accelerated decline in post-bronchodilator FEV1 (−0.41%; 95% CI −0.75, −0.06) and FVC (−0.31%; 95% CI −0.62, 0.01).

The authors added that these subgroups also were associated with certain patient histories.

“Compared to the average remission profile, adults with a Th2-high profile were more likely to have a history of allergic rhinitis and eczema, while adults with a Th2-low profile were more likely to be current smokers,” they noted.

The authors also found that BHR and a high tumor necrosis factor-alpha (TNF-α) levels during spontaneous remission were signs of a higher risk of relapse, though no such association was found between exhaled breath EBC NOx, nor was the latter associated with lung function decline.

The authors concluded their study confirmed that biomarkers can have meaningful value as a tool to assess patient risk. They said patients with BHR and high TNF-α or those with Th2-high or -low profiles might warrant closer follow-up and repeated spirometry.

“Studies with concurrent measures of systemic and airway inflammation and a wider range of biomarkers would help better identify those patients at risk of adverse outcomes,” they wrote.


Tan DJ, Lodge CJ, Walters EH, et al. Biomarkers of asthma relapse and lung function decline in adults with spontaneous asthma remission: A population-based cohort study. Allergy. Published online October 27, 2022. doi:10.1111/all.15566

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