medwireNews: The presence of type 2 inflammation, as indicated by elevated blood eosinophils (BEs) and fraction of exhaled nitric oxide (FeNO), is associated with accelerated decline in lung function in people with chronic airway disease, indicate Danish data.
The association between type 2 inflammation and lung function decline, measured by forced expiratory volume in 1 second (FEV1), was most pronounced in those with an asthma-like phenotype, the researchers note.
For example, among patients classified as having asthma with full reversibility (AR), FEV1 declined by a significant 1.6 mL/year with every 100 cells/μL increase in BEs and by 4.2 mL/year with every 10 ppb increase in FeNO. The corresponding declines in FEV1 in individuals who had asthma with persistent obstruction (APO) were a significant 3.5 mL/year and 5.9 mL/year.
By comparison, individuals with chronic obstructive pulmonary disease (COPD) had respective nonsignificant FEV1 declines of 1.0 mL/year and 1.5 mL/year.
“Future studies should investigate whether long-term treatment specifically targeting type-2 signalling could normalise lung function decline and halt disease progression in patients with asthma and COPD,” suggest Peter Lange, from Copenhagen University Hospital, and colleagues in Thorax.
They note that elevated type 2 inflammatory markers were also associated with greater lung function loss among individuals without airway disease.
“Therefore, it is possible that type-2 inflammation not only plays a role for the prognosis of individuals with established chronic airway disease but is also related to the natural course of FEV1 in individuals without a diagnosis of chronic airway disease,” the researchers comment.
The team studied data on 15,605 participants aged a median of 65 years from the Copenhagen General Population Study who had BE measurements taken over a 10-year period, with FeNO measurements also available in 2583 individuals.
The participants included 1519 with AR, 176 with APO, and 1232 with COPD. In addition, there were 1350 people with a ratio of FEV1 to forced vital capacity (FVC) below 0.70 but with no classifiable airflow limitation (NAL), due to lacking post-bronchodilator measurements and not wishing to participate in reversibility testing, and 11,328 controls who had no self-reported asthma and a ratio of FEV1 to FVC of at least 0.70.
They found that for all participants, FEV1 declined by a median 1.0 mL/year with every 100 cells/μL increase in BEs and by 3.2 mL/year with every 10 ppb increase in FeNO, after taking into account age, sex, height, smoking status and duration, and airway medication.
Moreover, the decline in FEV1 was a significant 49% greater when individuals had both increased BEs and FeNO, based on corresponding cutoffs of at least 300 cells/μL and at least 20 ppb, than when both measures were normal, at 27 mL/year versus 18 mL/year. This compared with a 21% greater decline for those who had increased levels in just one of the two measures.
When the patients were stratified for chronic airway disease, the declines in FEV1 among patients with increased BEs and FeNO relative to normal levels were 44 versus 24 mL/year in those with AR, 56 versus 16 mL/year in those with APO, 44 versus 32 mL/year in those with COPD, and 37 versus 27 mL/year in those with NAL. The differences were significant for patients with AR and APO, but not for those with COPD or NAL.
In an accompanying editorial, Nayia Petousi, from Oxford University Hospitals NHS Foundation Trust in the UK, and colleagues remark that the “clear message” from Lange and colleagues’ findings is that “phenotyping all patients (with asthma and COPD) by measuring their type-2 biomarkers is absolutely essential if one is interested in identifying those at risk of lung function decline, exacerbations, people remodelling and death.”
The editorialists also suggest that future approaches to limiting lung function decline should look “even more upstream” in the disease trajectory by identifying and treating type 2 inflammation early.
Doing so “will allow us to shake ourselves out of our current downstream firefighting approach to airway disease, where the focus is on the identification of damage and late intervention,” they conclude.
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Thorax 2024; doi:10.1136/thorax-2023-220972
Thorax 2024; doi:10.1136/thorax-2023-221329