Isabella Hornick , 2025-04-18 12:00:00
April 18, 2025
3 min read
Key takeaways:
- Between smokers with COPD and healthy nonsmokers, researchers found significantly more nasal IL-26 in the smoking plus COPD group
- This research will aid in finding new, simpler methods to assess for COPD.
Long-term smokers with and without mild to moderate COPD had raised nasal IL-26 levels, which were correlated to symptom/health impairment assessments, according to data published in Journal of Allergy and Clinical Immunology.
“These findings may allow us to develop the clinical means to safely assess the type of inflammation in the airways of patients with COPD by using the nose as a proxy, for both prognostic and therapeutic purposes,” Anders Lindén, MD, PhD, professor at the Institute of Environmental Medicine at Karolinska Institutet and senior physician at Karolinska University Hospital, told Healio. “However, additional studies will be needed before the everyday clinician can start using this new approach.”
In this study, Lindén and colleagues evaluated 16 long-term smokers with mild to moderate COPD, 20 long-term smokers without COPD and 14 healthy nonsmokers to uncover how IL-26 levels in the nose — measured via nasal lavage samples — differ between the three groups, as well as the role of T cells in IL-26 production in the nasal cavity.
“IL-26 has previously been linked to various inflammatory diseases, including COPD,” according to a press release from Karolinska Institutet.
Between the smokers with COPD and the healthy nonsmokers, researchers found significantly more nasal IL-26 in the smoking plus COPD group. Heightened nasal IL-26 was also found in smokers without COPD vs. healthy nonsmokers but did not reach significance.
When specifically assessing the group of smokers with COPD, the study noted a positive correlation between nasal IL-26 and FEV1/FVC.
“Thus, the more IL-26 there is in the nasal cavity, the lesser the chronic airflow limitation in these patients,” Lindén and colleagues wrote.
In terms of T cells, both CD4+ and CD8+ T cells were behind IL-26 protein expression, according to the study. Within these cells, co-expression of IL-15, IL-17A and IL-22 was noted in “a small portion” when evaluating the smoking plus COPD group.
“The general pattern is that the T cells producing IL-26 in the nasal cavity are relatively specialized in relation to type 3 cytokines,” Lindén and colleagues wrote.
Researchers further observed a significant negative correlation between IL-26 CD8+ T cells in smokers with COPD and FEV1. Dividing IL-26 into intracellular and extracellular also revealed a negative correlation between extracellular nasal IL-26 and relative mean fluorescence intensity (rMFI) of IL-26 CD8+ T cells, which researchers said, “is suggestive of cytotoxic T cells contributing to the release of extracellular IL-26 in the nasal cavity.”
In contrast to the negative correlations above, nasal IL-26 CD4+ and CD8+ T cells in smokers with COPD were each positively correlated with neutrophil counts in bronchoalveolar lavage samples. Nasal IL-26 in this group was also positively correlated with nasal IL-8, according to the study.
“Our current findings imply that IL-26 and IL-8 are mechanistically linked in the nasal cavity, just like in the bronchoalveolar space,” Lindén and colleagues wrote.
Switching to validated symptom/health impairment assessments, a negative correlation was reported between rMFI of nasal IL-26 CD8+ T cells and a transformed version of the modified Medical Research Council dyspnea scale score (score ≥ 1 = dyspnea) in long-term smokers. This T cell was also negatively correlated to the total St. George’s Respiratory Questionnaire score, according to the study.
“The statistically valid associations between nasal cytokine level and symptom scores were beyond our initial hypothesis,” Lindén told Healio.
Due to insufficient COPD therapy and the increasing prevalence of this disease beyond smokers, Lindén said this research will aid in finding new, simpler methods to assess COPD.
“It is important to realize that COPD is a chronic and deadly disorder for which current therapy is insufficient, partially because the therapy was originally developed for asthma and not for COPD,” Lindén told Healio. “Moreover, COPD does not only strike active smokers, and this inflammatory disorder is becoming more common at the global level, in many countries exceeding a prevalence of 10% among adults.
“For patients with severe COPD and exacerbations, the prognosis is as poor as that for lung cancer, whereas the prognosis for a former smoker that has mild to moderate disease is much better, although still very variable,” Lindén continued. “Thus, there is a need to improve the tools we have once the diagnosis is set, to be able to stratify patients according to risk and responsiveness to novel and more specific therapy that is under clinical development.”
Looking ahead, Lindén told Healio there are plans to evaluate patients with moderate to severe COPD.
“We now intend to perform a larger and prospective follow-up study on patients with more severe disease (COPD) and assess the clinical utility in terms of association with long term, clinical outcomes in registers,” Lindén said.
For more information:
Anders Lindén, MD, PhD, can be reached at anders.linden@ki.se.
Reference:
Perspective
The study by Arebro and colleagues provides important insight into the role of IL-26 as a potential immunologic marker in COPD. By demonstrating that IL-26 is produced by T cells in the nasal cavity and reflects inflammation and clinical symptoms associated with the lower airways, this work highlights the biological link between upper and lower airway compartments in COPD.
Given the substantial global burden of COPD, there is increasing recognition that spirometry alone does not capture the full complexity of the disease. Studies like this help broaden our understanding of COPD pathobiology and identify potential targets for more specific, tailored therapy.
Importantly, the use of nasal lavage as a surrogate for lower airway sampling offers a practical, noninvasive alternative to bronchoscopy. Correlations between nasal IL-26 levels, airflow limitation, neutrophilic inflammation and symptom scores strengthen its potential as an accessible biomarker for disease stratification.
Mechanistic insights into nasal T cell–derived IL-26 support its relevance in immune profiling and endotyping. As COPD care moves toward precision-guided approaches, this study reinforces the value of immunologic markers in guiding treatment strategies beyond symptom control alone.
Seyedmohammad Pourshahid, MD, MPH
Disclosures: Pourshahid reports no relevant financial disclosures.
Sources/Disclosures
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Disclosures:
The Swedish Heart-Lung Foundation, the Swedish Research Council, Region Stockholm, the Swedish Society for Respiratory Medicine and AstraZeneca funded this study. The authors report no relevant financial disclosures.