Expression of TSLP Isoforms in Asthma

TSLP and Its Isoforms (Short and Long Form TSLP) in Different Asthma Phenotypes

Asthma is a heterogeneous disease characterized by chronic airway inflammation, leading to variable airflow obstruction, bronchial hyperresponsiveness, excessive mucus secretion, and, consequently, structural airway remodeling. Asthma is defined by the presence of symptoms such as wheezing, dyspnea, chest tightness, and cough, with variable intensity and frequency.

Thymic stromal lymphopoietin (TSLP) is a cytokine produced primarily by epithelial cells in the lungs. Two distinct isoforms of TSLP have been identified: a long form (lfTSLP) and a short form (sfTSLP). The long isoform is induced during inflammatory conditions and promotes a T2-dependent immune response. In contrast, the short isoform is believed to exert homeostatic and anti-inflammatory functions and exhibits antimicrobial properties.

Studies have demonstrated an association between elevated serum and airway TSLP levels and increased disease severity, as well as reduced spirometric parameters. However, the literature contains limited data regarding the expression of TSLP isoforms across different asthma phenotypes and their relationship with the degree of disease control.

The goal of this study is:

1. To assess the expression of TSLP protein and TSLP mRNA, including its isoforms (sfTSLP and lfTSLP), in serum and in airway-derived samples (nasal epithelial cells),
2. To compare these levels among patients with different asthma phenotypes (allergic and non-allergic asthma; eosinophilic, neutrophilic, and paucigranulocytic asthma; early-onset and late-onset asthma; obesity-associated asthma; cough-variant asthma), as well as between patients with asthma and healthy controls.
3. To analyze the correlations between the expression of TSLP isoforms (sfTSLP and lfTSLP) and asthma severity, level of disease control (as measured by the Asthma Control Questionnaire [ACQ]), pulmonary function parameters, blood eosinophil count and other clinical parameters.

1. Inclusion criteria

   • age > 18 years, without the upper age limit,
   • asthma (diagnosis in accordance with the GINA 2023 guidelines),

2. Exclusion criteria

   • other respiratory diseases (e.g., chronic obstructive pulmonary disease [COPD]);
   • active cigarette smoking or a smoking history of >10 pack-years;
   • active malignancy;
   • active pulmonary tuberculosis or active respiratory tract infection;
   • use of antibiotics within 4 weeks prior to study enrollment;
   • current long-term home oxygen therapy (>15 hours per day);
   • current treatment with monoclonal antibody therapies (e.g., omalizumab, mepolizumab, reslizumab, dupilumab, tezepelumab, or other biologics);
   • pregnancy.