Allergy Asthma Immunol Res.  2019 Jan;11(1):79-89. 10.4168/aair.2019.11.1.79.

Association Between Epithelial Cytokines and Clinical Phenotypes of Elderly Asthma

• Ulambayar
• Lee SH
• Yang EM
• Ye YM
• Park HS

• KMID: 2426787
• DOI: http://doi.org/10.4168/aair.2019.11.1.79

Abstract

PURPOSE
Asthma in the elderly has different clinical features including more severe phenotypes with higher comorbidities. Epithelial cells are known to initiate innate/adaptive immune responses in asthmatic airways. We investigated clinical features and epithelial derived cytokine levels in elderly asthmatics compared to non-elderly asthmatics in a cross-sectional cohort of adult asthmatics in order to further understand its pathogenic mechanisms.
METHODS
A total of 1,452 adult asthmatics were enrolled from a single tertiary hospital and were classified into 2 groups: 234 elderly (≥ 60 years at initial diagnosis) and 1,218 non-elderly (< 60 years at initial diagnosis) asthmatics. Asthma-related clinical parameters were compared between the 2 groups. Serum levels of epithelial cell-derived cytokines including interleukin (IL)-31, IL-33, IL-8, eotaxin-2, transforming growth factor beta 1 (TGF-β1) and periostin were measured by enzyme-linked immunosorbent assay.
RESULTS
Significantly higher prevalence rates of late-onset asthma (onset age ≥ 40 years) and severe asthma, as well as the lower rate of atopy, blood/sputum eosinophil counts, total immunoglobulin E and eosinophil cationic protein levels were noted in elderly asthmatics compared to non-elderly asthmatics (P < 0.05, respectively). The forced expiratory volume in 1 second (FEV1, % predicted) level tended to be lower in elderly asthmatics (P = 0.07). In addition, serum IL-33 and IL-31 levels were significantly lower in elderly asthmatics, while no differences were found in the serum level of IL-8, eotaxin-2, TGF-β1 or periostin. Among elderly asthmatics, subjects with severe asthma had lower FEV1 (% predicted) value, but showed significantly higher serum levels of eotaxin-2 and TGF-β1, than those with non-severe asthma (P < 0.05 for each).
CONCLUSIONS
These findings suggest that age-related changes of epithelial cell-derived cytokines may affect clinical phenotypes and severity of elderly asthma: decreased levels of IL-33 and IL-31 may contribute to less Th2 phenotype, while increased levels of eotaxin-2 and TGF-β1 may contribute to severity.

Keyword

Asthma; older adults; epithelial cells; interleukin-33; interleukin-31; eotaxin-2, TGF-beta1

MeSH Terms

Adult
Aged*
Asthma*
Chemokine CCL24
Cohort Studies
Comorbidity
Cytokines*
Enzyme-Linked Immunosorbent Assay
Eosinophil Cationic Protein
Eosinophils
Epithelial Cells
Forced Expiratory Volume
Humans
Immunoglobulin E
Immunoglobulins
Interleukin-33
Interleukin-8
Interleukins
Phenotype*
Prevalence
Tertiary Care Centers
Transforming Growth Factor beta
Chemokine CCL24
Cytokines
Eosinophil Cationic Protein
Immunoglobulin E
Immunoglobulins
Interleukin-33
Interleukin-8
Interleukins
Transforming Growth Factor beta

Figure

• 

  Fig. 1 Comparison of serum levels of IL-33 and IL-31 between EA and NEA patients. Serum cytokine levels were measured by ELISA. Each mean value is represented and P values were analyzed by the Mann-Whitney U test. P < 0.05 was considered significantly different. IL, interleukin; EA, elderly asthma; NEA, non-elderly asthma; ELISA, enzyme-linked immunosorbent assay.

• 

  Fig. 2 Comparison of serum levels of eotaxin-2 and TGF-β1 according to severity in elderly asthma patients. Severe asthma was defined according to International ERS/ATS guideline. Serum cytokine levels were measured by ELISA. Each mean value is represented and P values were analyzed by the Mann-Whitney U test. P < 0.05 was considered significantly different. TGF-β1, transforming growth factor beta 1; ERS/ATS, European Respiratory Society/American Thoracic Society; ELISA, enzyme-linked immunosorbent assay; SEA, severe elderly asthma; NSEA, non-severe elderly asthma.

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