# Effect of Aspirin Challenge on Innate Lymphoid Cells in Asthma Patients With Aspirin Hypersensitivity

**Authors:** Radosław Kacorzyk, Bogdan Jakiela, Alicja Maciejska, Agnieszka S. Węgrzyn, Adam Ćmiel, Marek Sanak, Lucyna Mastalerz

PMC · DOI: 10.1002/eji.70020 · European Journal of Immunology · 2025-08-04

## TL;DR

This study found that aspirin-induced bronchospasm in asthma patients increases blood ILC1s and reduces sputum eicosanoids, suggesting a role for ILC1s in this allergic reaction.

## Contribution

The study identifies a specific increase in blood ILC1s during aspirin-induced bronchospasm in N-ERD patients.

## Key findings

- Blood ILC1 count and percentage significantly increased during aspirin-induced bronchospasm.
- Sputum ILC counts showed no significant changes due to low detection numbers.
- Sputum eicosanoid levels, including PGE2 and PGD2, decreased during bronchospasm.

## Abstract

Previous studies confirmed increased group 2 innate lymphoid cell (ILC2s) count in nasal scrapings, alongside a reduced blood ILC2 count, in patients with nonsteroidal anti‐inflammatory drug‐exacerbated respiratory disease (N‐ERD) after intranasal administration of cyclooxygenase‐1 inhibitors. This study aimed to assess the role of blood and sputum ILCs in N‐ERD patients during oral aspirin‐induced bronchospasm and to compare patients with eosinophilic and noneosinophilic airway inflammatory phenotypes of asthma. Induced sputum, blood, and urine samples were collected in 24 patients with confirmed N‐ERD at baseline and during aspirin‐induced bronchospasm. Sputum and blood ILC counts were evaluated using flow cytometry. There was a significant increase in blood ILC1 count (p < 0.001) and percentage (p = 0.003) during aspirin‐induced bronchospasm. No significant changes in sputum ILCs were observed, but the number of detected ILCs was very low. There was a significant reduction in induced sputum supernatant (ISS) levels of prostaglandins PGE2 (p = 0.004) and PGD2 (p = 0.045), leukotriene B4 (p = 0.045), and 15‐oxo‐eicosatetraenoic acid (p = 0.045) during aspirin‐induced bronchospasm. Blood ILC1 count is increased during oral aspirin‐induced bronchospasm in patients with N‐ERD, but sputum ILC count at baseline is very low. Therefore, no reliable changes in sputum ILC counts can be detected during bronchospasm.

In N‐ERD patients, oral aspirin‐induced bronchospasm is associated with increased blood group 1 innate lymphoid cells (ILC1s), decreased sputum eicosanoids, and increased urinary leukotriene E4 (LTE4), suggesting a potential role of blood ILC1s in aspirin‐induced bronchoconstriction.

## Linked entities

- **Chemicals:** aspirin (PubChem CID 2244), PGE2 (PubChem CID 5280360), PGD2 (PubChem CID 448457), leukotriene B4 (PubChem CID 5280492), leukotriene E4 (PubChem CID 5280879)
- **Diseases:** asthma (MONDO:0004979)

## Full-text entities

- **Genes:** IGHE (immunoglobulin heavy constant epsilon) [NCBI Gene 3497] {aka IgE}, PTPRC (protein tyrosine phosphatase receptor type C) [NCBI Gene 5788] {aka B220, CD45, CD45R, GP180, IMD105, L-CA}, GATA3 (GATA binding protein 3) [NCBI Gene 2625] {aka HDR, HDRS}, IL22 (interleukin 22) [NCBI Gene 50616] {aka IL-21, IL-22, IL-D110, IL-TIF, ILTIF, TIFIL-23}, IL25 (interleukin 25) [NCBI Gene 64806] {aka IL17E}, PTGDR2 (prostaglandin D2 receptor 2) [NCBI Gene 11251] {aka CD294, CRTH2, DL1R, DP2, GPR44}, PRSS33 (serine protease 33) [NCBI Gene 260429] {aka EOS}, IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta}, SERPINB2 (serpin family B member 2) [NCBI Gene 5055] {aka HsT1201, PAI, PAI-2, PAI2, PLANH2}, CCR3 (C-C motif chemokine receptor 3) [NCBI Gene 1232] {aka C C CKR3, CC-CKR-3, CD193, CKR 3, CKR3, CMKBR3}, IL7R (interleukin 7 receptor) [NCBI Gene 3575] {aka CD127, CDW127, IL-7R-alpha, IL-7Ralpha, IL7RA, IL7Ralpha}, TBX21 (T-box transcription factor 21) [NCBI Gene 30009] {aka IMD88, T-PET, T-bet, TBET, TBLYM}, CD4 (CD4 molecule) [NCBI Gene 920] {aka CD4mut, IMD79, Leu-3, OKT4D, T4}, CCL27 (C-C motif chemokine ligand 27) [NCBI Gene 10850] {aka ALP, CTACK, CTAK, ESKINE, ILC, PESKY}, KIT (KIT proto-oncogene, receptor tyrosine kinase) [NCBI Gene 3815] {aka C-Kit, CD117, MASTC, PBT, SCFR}, IL17A (interleukin 17A) [NCBI Gene 3605] {aka CTLA-8, CTLA8, IL-17, IL-17A, IL17, ILA17}, IL4 (interleukin 4) [NCBI Gene 3565] {aka BCGF-1, BCGF1, BSF-1, BSF1, IL-4}, CLCA1 (chloride channel accessory 1) [NCBI Gene 1179] {aka CACC, CACC1, CLCRG1, CaCC-1, GOB5, hCLCA1}, CST1 (cystatin SN) [NCBI Gene 1469], IL2 (interleukin 2) [NCBI Gene 3558] {aka IL-2, TCGF, lymphokine}, IL13 (interleukin 13) [NCBI Gene 3596] {aka IL-13, P600}, CYSLTR1 (cysteinyl leukotriene receptor 1) [NCBI Gene 10800] {aka CYSLT1, CYSLT1R, CYSLTR, HMTMF81}, IL12B (interleukin 12B) [NCBI Gene 3593] {aka CLMF, CLMF2, IL-12B, IMD28, IMD29, NKSF}, IL33 (interleukin 33) [NCBI Gene 90865] {aka C9orf26, DVS27, IL1F11, NF-HEV, NFEHEV}, CLC (Charcot-Leyden crystal galectin) [NCBI Gene 1178] {aka GAL10, Gal-10, LGALS10, LGALS10A, LPPL_HUMAN}, POSTN (periostin) [NCBI Gene 10631] {aka OSF-2, OSF2, PDLPOSTN, PN}, IL5 (interleukin 5) [NCBI Gene 3567] {aka EDF, IL-5, TRF}, GAPDH (glyceraldehyde-3-phosphate dehydrogenase) [NCBI Gene 2597] {aka G3PD, GAPD, HEL-S-162eP}, PTGDS (prostaglandin D2 synthase) [NCBI Gene 5730] {aka L-PGDS, LPGDS, PDS, PGD2, PGDS, PGDS2}, TSLP (thymic stromal lymphopoietin) [NCBI Gene 85480], IFNG (interferon gamma) [NCBI Gene 3458] {aka IFG, IFI, IMD69}, COX1 (cytochrome c oxidase subunit I) [NCBI Gene 4512] {aka COI, MTCO1}
- **Diseases:** aspirin (MESH:D055963), N (MESH:C536108), airway eosinophilia (MESH:D004802), CRSwNP (MESH:D009298), Bronchospasm (MESH:D001986), chronic rhinosinusitis (MESH:D000092562), N-ERD (MESH:D018450), hypersensitivity (MESH:D004342), respiratory disease (MESH:D012140), trauma (MESH:D014947), inflammation (MESH:D007249), respiratory symptoms (MESH:D012818), type 2 (T2) (MESH:D003924), Asthma (MESH:D001249), ILCs (MESH:D016399), eosinophilic (MESH:D017681)
- **Chemicals:** LTC4 (MESH:D017997), PGE2 (MESH:D015232), leukotrienes (MESH:D015289), LTD4 (MESH:D017998), prostaglandins (MESH:D011453), LTB4 (MESH:D007975), Lipid (MESH:D008055), 5-HETE (MESH:C022022), cysteinyl leukotrienes (MESH:C112381), LTE4 (MESH:D017999), 15-oxo-eicosatetraenoic acid (-), 9alpha,11beta-PGF2 (MESH:D015237), 12- hydroxyeicosatetraenoic acid (MESH:D019377), prostaglandin D2 (MESH:D015230), Aspirin (MESH:D001241), creatinine (MESH:D003404), Eicosanoids (MESH:D015777)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

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## References

51 references — full list in the complete paper: https://tomesphere.com/paper/PMC12319354/full.md

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Source: https://tomesphere.com/paper/PMC12319354