Th2-High Severe Asthma with Hypereosinophilia in the Spectrum of Type 2 Inflammatory Diseases
Abstract
1. Introduction
2. T2-High Asthma
2.1. Hypereosinophilia and T2-High Asthma
2.2. Other T2 Conditions
2.3. EGPA and Asthma
2.4. HES and Asthma
3. Treatment of Hypereosinophilic Asthma
4. Discussion
5. Conclusions
6. Summary
Funding
Conflicts of Interest
Abbreviations
ABL1 | v-abl Abelson murine leukemia viral oncogene homolog 1 |
ABPA | allergic bronchopulmonary aspergillosis |
ACEI | Angiotensin-converting-enzyme inhibitor |
ACQ | Asthma Control Questionnaire |
ACR/EULAR | American College of Rheumatology and European League Against Rheumatism |
AED | Anticonvulsant drug |
AD | atopic dermatitis |
ARV | antiretroviral drug |
AR | allergic rhinitis |
Ath | artery thrombosis |
ATS | American Thoracic Society |
BTP | bronchothermoplasty |
CEL | chronic eosinophilic leukemia |
CCL | C-C motif chemokine ligand |
CEP | chronic eosinophilic pneumonia |
CNPG | chronic prurigo nodularis |
COX-1 | cyclooxygenase-1 |
CRSwNP | chronic rhinosinusitis with nasal polyps |
CTX | cyclophosphamide |
CU | chronic urticaria |
CSU | chronic spontaneous urticaria |
CXCL | C-X-C motif ligand |
CystLTR | cysteinyl leukotriene receptor |
DRESS | drug reaction with eosinophilia and systemic symptoms |
DVT | deep vein thrombosis |
EGID | eosinophilic gastrointestinal disease |
EGPA | eosinophilic granulomatosis with polyangiitis |
EN | erythema nodosum |
EOS | eosinophil |
EoE | eosinophilic esophagitis |
EP | eosinophilic pneumonia |
EPO | (human) erythropoietin |
ERS | European Respiratory Society |
ES | eosinophilic sinusitis |
ET | essential thrombocytopenia |
FA | food allergy |
FeNO | fractional exhaled nitric oxide |
FGFR | fibroblast growth factor receptor |
FLT3 | FMS-like tyrosine kinase 3 |
GE | eosinophilic gastroenteritis |
GERD | gastroesophageal reflux disease |
GINA | Global Initiative for Asthma |
GM-CSF | granulocyte-macrophage colony-stimulating factor |
HE | hypereosinophilia |
HES | hypereosinophilic syndrome |
HESN | HES neoplasia |
HESR | HES reactive |
HESI | HES idiopathic |
HESFA | HES familial |
HU | hydroxyurea |
ICI | immune checkpoints inhibitor |
ICS | inhaled corticosteroid |
IL | interleukin |
IL-5R | interleukin-5 receptor |
ILC | innate lymphoid cell |
IM | immunomodulator |
JAK | Janus kinase |
JAKi | Janus Kinase inhibitor |
KI | kinase inhibitor |
KIT | KIT proto-oncogene, encoding tyrosine kinase receptor |
LABA | long-acting beta2-agonist |
LHEA | late-onset hypereosinophilic asthma |
LTRA | leukotriene receptor agonist |
MAb | monoclonal antibody |
MART/SMART | maintenance and reliever therapy/single-inhaler MART |
MIRACLE trial | Multicenter InSync Randomized Clinical Evaluation trial |
MPN | myeloproliferative neoplasm |
N-ERD | NSAID-exacerbated respiratory disease |
NEST | The Nucala Effectiveness Study |
NP | nasal polyposis |
NSAID | Non-steroidal anti-inflammatory drug |
OCS | oral corticosteroid |
OM | otitis media |
OSM | oncostatin M |
PCM1 | pericentriolar material 1 |
PDE5 | phosphodiesterase 5 |
PDGFR | platelet-derived growth factor receptor |
PE | pulmonary embolism |
PN | prurigo nodularis |
PPI | proton-pump inhibitor |
PV | polycythemia vera |
REALTI-A | The REAL-world effectiveness of mepolizumab In paTIent care—Asthma |
ReQualBi study | Re-Qualification of the asthma patient on Biologic therapy study |
RTX | rituximab |
SABA | short-acting β2-agonist |
SA | severe asthma |
SEM | systemic eosinophilic manifestation |
STAT | signal transducer and activator of transcription pathway |
TKI | tyrosine kinase inhibitor |
TSLP | Thymic stromal lymphopoietin |
T2 | Type 2 |
VCAM-1 | vascular cell adhesion molecule 1 |
VKC | vernal keratoconjunctivitis |
WARF | warfarin |
WBC | white blood cell |
WHO | World Health Organization |
XOI | xanthine oxidase inhibitor |
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Patient Details [(M) Male/(F) Female (Age)] | Highest EOS Count [cells/µL] | Comorbidities | Previous Treatment | Administered Medication | [Source] |
---|---|---|---|---|---|
M (51) | >1700 | CRSwNP | OCS, omalizumab, BTP | benralizumab | [37] |
M (55) | 7200 | AR | SABA, OCS | ICS/LABA, LTRA, SABA | [56] |
F (36) | 5540 | CU, MPN | HU, WARF, ICS | OCS | [7] |
F (54) | 4510 | T cell clone | ICS | OCS | |
M (62) | 2000 | PE, DVT | ICS, WARF | OCS | |
4 M 11 F (mean 43.7) | - 1,2 | EP, ES, GE, OM | - 1 | OCS | [31] |
F (32) | 6540 | CRSwNP, AR | - 1 | polypectomy | [36] |
F (22) | 2125 | CEP, AR | ICS/LABA, OCS | OCS, dupilumab | [60] |
F | 1810 | CRSwNP, GERD | OCS, omalizumab, mepolizumab | OCS, omalizumab, benralizumab | [71] 3,4 |
M | 1550 | NP, VKC, epilepsy | OCS, omalizumab, mepolizumab | OCS, omalizumab, mepolizumab, benralizumab | |
M | 5000 | NP | OCS, omalizumab, mepolizumab | OCS, omalizumab, mepolizumab, benralizumab | |
M | 1700 | CRSwNP, CU | OCS, omalizumab, mepolizumab | OCS, omalizumab, mepolizumab, benralizumab | |
M | 40,400 | CRSwNP, AD | OCS, omalizumab, mepolizumab | OCS, IM, omalizumab, mepolizumab, benralizumab | |
F | 2100 | NP | OCS, omalizumab, mepolizumab | OCS, omalizumab, mepolizumab, benralizumab |
Condition | Mild (%) | Moderate (%) | Severe (%) | Asthma Cases with HE |
---|---|---|---|---|
Allergic diseases | 59.8 | 10.8 | - 1 | +++ |
Parasitic infestation | 22.7 | 29.7 | 14.3 | - |
Drug allergy | 13.4 | 37.8 | 14.3 | - |
HES | 1.0 | 8.1 | 21.4 | - |
EGPA | 1.0 | 2.7 | 28.6 | - |
ABPA | 1.0 | 2.7 | 7.1 | - |
CEP | - 1 | 8.1 | 7.1 | + |
EGID | 1.0 | - 1 | 7.1 | + |
Drug | Used in | Efficacy | [Source] | ||
---|---|---|---|---|---|
medication resolving HE | mepolizumab | SA, CRSwNP, EGPA, HES | SA | 83% reduction at 12 months 1 | [63] |
HES | 92% reduction at 32 weeks | ||||
benralizumab | SA, HES, EoE, CRSwNP 3 | HES | down to 0 cells/μL by week 4 2 | [25] | |
612.78 cells reduction at 12 months | [80] | ||||
reslizumab | HES 4 | 5438 to <500 cells/μL at 21 months | [81] | ||
omalizumab | HESI | 4310 to 1000 cells/μL at 17 months | [82] | ||
7010 to 2230 cells/μL at 3 months | |||||
OCS | HESI | 2100 to <500 cells/μL at 6 months 5 | [83] | ||
asthma medication resulting in HE | dupilumab | SA, CSU | 280 to 310 cells/μL in 4 weeks 6 | [47] | |
400 to 4900 cells/μL in 4 weeks | [58] | ||||
500 to 2000 cells/μL in 16 weeks | |||||
600 to 9000 cells/μL in 16 weeks | |||||
800 to 2500 cells/μL in 16 weeks | |||||
50 to 5000 cells/μL in 16 weeks | |||||
300 to 2000 cells/μL in 6 months 6 | |||||
750 to 4880 cells/μL in >2 months 7 | [55] |
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Malaya, E.; Marszałek, K.; Kuna, P.; Kupczyk, M.; Panek, M. Th2-High Severe Asthma with Hypereosinophilia in the Spectrum of Type 2 Inflammatory Diseases. Int. J. Mol. Sci. 2025, 26, 5342. https://doi.org/10.3390/ijms26115342
Malaya E, Marszałek K, Kuna P, Kupczyk M, Panek M. Th2-High Severe Asthma with Hypereosinophilia in the Spectrum of Type 2 Inflammatory Diseases. International Journal of Molecular Sciences. 2025; 26(11):5342. https://doi.org/10.3390/ijms26115342
Chicago/Turabian StyleMalaya, Elizabeth, Kamil Marszałek, Piotr Kuna, Maciej Kupczyk, and Michał Panek. 2025. "Th2-High Severe Asthma with Hypereosinophilia in the Spectrum of Type 2 Inflammatory Diseases" International Journal of Molecular Sciences 26, no. 11: 5342. https://doi.org/10.3390/ijms26115342
APA StyleMalaya, E., Marszałek, K., Kuna, P., Kupczyk, M., & Panek, M. (2025). Th2-High Severe Asthma with Hypereosinophilia in the Spectrum of Type 2 Inflammatory Diseases. International Journal of Molecular Sciences, 26(11), 5342. https://doi.org/10.3390/ijms26115342