Asthma and COPD – Who benefits from anti-IL-33 therapy?

Interleukin-33 (IL-33) is considered an important driver of inflammation in asthma and COPD, which leads to chronic lung damage and recurrent infections. In order to further characterise the clinical significance of IL-33 at the site of action, scientists at the DZL sites ARCN and TLRC measured IL-33 levels in the sputum from the airways of patients and compared them with clinical data. They found that ex-smokers might benefit most from anti-IL-33 therapy.

It was previously known that IL-33 is increasingly produced in people suffering from asthma or COPD. For this reason, various companies are conducting clinical trials to test the extent to which symptoms can be alleviated by preventing IL-33 from binding to its receptor. Surprisingly, a dependence on the smoking status of the test subjects was found.

Surprising results in smokers and ex-smokers

These results were reproduced and clarified in the current study led by Dr Mustafa Abdo and Dr Frauke Pedersen (both from the LungenClinic Grosshansdorf). The IL-33 levels in the sputum of severe asthmatics differed significantly from those of healthy subjects, as did those of COPD patients. In the latter, there were clear dependencies on two clinical parameters: patients in more severe stages of the disease had higher IL-33 levels than those in earlier stages. Interesting results were found in smokers: COPD patients who had quit smoking showed significantly higher sputum IL-33 levels than active smokers. This may be due to the fact that active smokers have a more damaged airway mucosa, which normally serves as a reservoir for IL-33.

Clinical studies already underway

Mustafa Abdo interprets these findings as follows: ‘Our study provides a precise phenotyping of IL-33 production, which is currently being investigated in clinical Phase III trials. It facilitates the selection of patients who may benefit from this targeted therapy.’

The study was a collaboration between the DZL sites ARCN and TLRC. The research team published the results in the European Respiratory Journal, a leading journal in the field.

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Original publication: Abdo M, Pedersen F, Kirsten AM, Trinkmann F, Groth EE, Bahmer T, Watz H, Rabe KF. Association of airway inflammation and smoking status with IL-33 level in sputum of patients with asthma or COPD. Eur Respir J. 2024 Aug 15.  doi: 10.1183/13993003.00347-2024.

Source: ARCN