Severe Eosinophilic Asthma: Does Smoking History Affect Treatment Response?

In patients with severe asthma, former smoking history is associated with eosinophilic airway inflammation and activation, relative insensitivity to steroids, and airway autoimmunity, according to a study published in the European Respiratory Journal.

Although the association between smoking and autoimmunity was hypothesized more than 15 years ago, this association in patients with asthma has not been fully investigated. Therefore, researchers assessed the impact of smoking on airway levels of eosinophilic inflammation and activation, and autoreactivity to eosinophil peroxidase (EPX) and macrophage scavenger receptors in patients with severe eosinophilic asthma. Because severe eosinophilic asthma is characterized by a relative refractoriness to steroids, the impact of smoking on the response to systemic steroids was also investigated.

A total of 132 patients with severe asthma were included in the study, with 39 patients (29.5%) having a ≥10 pack years of smoking history (36 former smokers and 3 current smokers) and 93 patients (70.5%) having a <10 pack years exposure. The investigators found that eosinophilic airway inflammation was more prevalent among patients with ≥10 pack years smoking history (66.7%) compared with patients with <10 pack years smoking history (38.7%, P=.03), as was the level of free eosinophil granules (P =.001) and both anti-EPX and anti-macrophage receptor with collagenous structure (MARCO) (P <.05 and  P<.0001, respectively). The researchers also found that omitting current smokers did not affect these associations. In addition, prednisolone reduced but did not normalize sputum eosinophils in patients with a ≥10 pack years smoking history.

“In conclusion, former smoking exposure was associated with activated airway eosinophils and autoreactivity towards eosinophils and macrophages, as well as an incomplete anti-inflammatory response to systemic corticosteroids,” stated the researchers. “Overall, our findings suggest the existence of a more active and exacerbation-prone phenotype of severe eosinophilic asthma among predominantly former smokers that is potentially more treatment refractory,” they added.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures. 

Reference

Klein DK, Silberbrandt A, Frøssing L, et al. Impact of former smoking exposure on airway eosinophilic activation and autoimmunity in patients with severe asthma. Eur Respir J. Published online March 2, 2022. doi:10.1183/13993003.02446-2021