# The relationship of chemokine levels and the type of symptoms caused by NSAIDs or alcohol in patients with NSAIDs-exacerbated respiratory disease

**Authors:** Karolina Frachowicz-Guerreiro, Adrian Gajewski, Maciej Chałubiński, Aleksandra Wardzyńska

PMC · DOI: 10.3389/fimmu.2025.1722171 · Frontiers in Immunology · 2026-01-07

## TL;DR

This study explores how chemokine levels relate to symptoms caused by NSAIDs or alcohol in patients with a specific asthma condition called N-ERD.

## Contribution

The study identifies distinct chemokine profiles associated with different symptom types in N-ERD patients following NSAID or alcohol exposure.

## Key findings

- N-ERD patients had higher CCL17/TARC levels in exhaled breath condensate compared to controls.
- Serum CCL17/TARC levels were lower in N-ERD patients with dyspnea after NSAIDs.
- Alcohol symptoms in N-ERD correlated with lower urinary CCL5/RANTES levels.

## Abstract

Nonsteroidal anti-inflammatory drug (NSAID)-exacerbated respiratory disease (N-ERD) is an asthma phenotype with a complex pathogenesis involving chemokine-mediated inflammation. This study aimed to evaluate the association between chemokine levels and symptoms triggered by NSAIDs and alcohol in patients with N-ERD.

Seventy-two subjects (41 N-ERD, 20 NSAID-tolerant asthma [NTA], and 11 healthy controls) were assessed via questionnaire, lung function tests, and measurement of selected chemokines in serum, urine, and exhaled breath condensate (EBC).

N-ERD patients exhibited significantly higher CCL17/TARC levels in EBC compared to controls (p<0.001). Both N-ERD and NTA groups had elevated serum CCL5/RANTES levels relative to controls (p=0.002 and p=0.04, respectively). Respiratory symptoms after alcohol consumption were reported by 48% of N-ERD patients, significantly more frequent than in controls (p<0.05), with dyspnea more common in N-ERD than NTA (p=0.03). In N-ERD patients, serum CCL17/TARC levels were lower in those experiencing dyspnea after NSAIDs (p=0.03), while serum CXCL10/IP-10 levels were higher in patients with mixed (not only respiratory) symptoms (p=0.015). Alcohol symptoms in N-ERD correlated with lower urinary CCL5/RANTES levels (p=0.01). Nasal blockage after alcohol was associated with reduced CCL17/TARC in EBC (p=0.01), and dyspnea after alcohol correlated with lower serum CCL26/Eotaxin-3 (p=0.047).

Chemokine profiles differ according to symptom type following NSAID or alcohol exposure in N-ERD patients. These findings highlight the heterogeneity of N-ERD and suggest distinct inflammatory pathways linked to clinical presentations.

## Linked entities

- **Proteins:** CCL17 (C-C motif chemokine ligand 17), CCL17 (C-C motif chemokine ligand 17), CCL5 (C-C motif chemokine ligand 5), CCL5 (C-C motif chemokine ligand 5), CXCL10 (C-X-C motif chemokine ligand 10), CXCL10 (C-X-C motif chemokine ligand 10), CCL26 (C-C motif chemokine ligand 26)
- **Chemicals:** alcohol (PubChem CID 702)
- **Diseases:** asthma (MONDO:0004979)

## Full-text entities

- **Genes:** CCL17 (C-C motif chemokine ligand 17) [NCBI Gene 6361] {aka A-152E5.3, ABCD-2, SCYA17, TARC}, CCL26 (C-C motif chemokine ligand 26) [NCBI Gene 10344] {aka IMAC, MIP-4a, MIP-4alpha, SCYA26, TSC-1}, CXCL10 (C-X-C motif chemokine ligand 10) [NCBI Gene 3627] {aka C7, IFI10, INP10, IP-10, SCYB10, crg-2}, CCL5 (C-C motif chemokine ligand 5) [NCBI Gene 6352] {aka D17S136E, RANTES, SCYA5, SIS-delta, SISd, TCP228}
- **Diseases:** Respiratory symptoms (MESH:D012818), dyspnea (MESH:D004417), respiratory (MESH:D012131), asthma (MESH:D001249), respiratory disease (MESH:D012140), Nasal blockage (MESH:D015508), inflammation (MESH:D007249), N (MESH:C536108)
- **Chemicals:** N (MESH:D009584), Alcohol (MESH:D000438)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12819236/full.md

## References

22 references — full list in the complete paper: https://tomesphere.com/paper/PMC12819236/full.md

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Source: https://tomesphere.com/paper/PMC12819236