Study population
This study was based on the data obtained from ‘the FD asthma database’, which contains the clinical data of 1443 asthmatic patients (≥ 18 years old) who regularly visited the outpatient clinic of the Department of Allergy and Respiratory Medicine at The Fraternity Memorial Hospital in 2015. The database included demographic data, comorbidities, spirometry data (pre-bronchodilator values) under stable conditions of asthma, laboratory data under stable conditions of asthma, characteristics of asthma, types of controllers used under stable conditions, and the number of exacerbations. The duration of asthma was based on patient-reported data. The inclusion criteria for the database were (1) asthma diagnosed using the Global Initiative for Asthma (GINA) guidelines; (2) regular visits to our hospital and regular use of controller medication for asthma for ≥ 2 years before enrolment; (3) available spirometry data obtained under stable conditions; and (4) no other respiratory diseases potentially affecting the spirometry data, such as old tuberculosis, diffuse emphysema, bronchiolitis, interstitial lung disease, or diffuse lung diseases. Clinical and laboratory data were obtained from electronic medical records to establish the database.
Data of obese patients were extracted from the FD asthma database. We used the criteria for obesity for Japanese participants defined by the Japan Society for the Study of Obesity (BMI ≥ 25 kg/m2, criterion for obesity for Japanese people). The cut-off level was established because the optimal cut-off BMI for maximising the sensitivity and specificity for obesity-related disorders is 25 kg/m2 in Japanese people26.
Study design
We classified the enrolled obese asthmatic patients into two groups: patients with obese asthma with positive type-2 inflammation markers (T2, peripheral blood eosinophil counts ≥ 300/µL or a specific allergen detected) and patients with obese asthma with negative type-2 inflammation markers (NT2, peripheral blood eosinophil counts < 300/µL, and no specific allergen detected), and data were compared between the groups. This study was approved by The Fraternity Memorial Hospital Research Ethics Committee and performed according to the Declaration of Helsinki.
Data collection
All data were obtained from the FD asthma database. Severe asthma was defined based on the European Respiratory Society/American Thoracic Society (ERS/ATS) guidelines for severe asthma27. “Severe acute exacerbation of asthma” was defined as an event requiring an emergency room visit and hospitalisation for treatment with systemic corticosteroids or increased systemic corticosteroids from a stable maintenance dose for ≥ 3 days28. The annual exacerbation ratio was defined as the total number of severe acute exacerbations /total duration of the observed period (years).
Collection and analysis of serum samples
Obese asthmatic patients were recruited from the Department of Allergy and Respiratory Medicine outpatient at Fraternity Memorial Hospital between April 2019 and December 2019 for this analysis. Patients who satisfied the following criteria were included: (1) had obesity; (2) had asthma diagnosed according to the Global Initiative for Asthma (GINA) guidelines; (3) had received regular medication for at least 1 year before enrolment; and (4) had no infection or asthma exacerbations requiring the administration of systemic corticosteroids within 4 weeks of enrolment. In addition, peripheral blood eosinophil counts and IgE levels under stable conditions of asthma were collected from the medical records.
Serum samples were collected from patients and stored at − 80 °C until analysis. Serum leptin and plasminogen activator inhibitor-1 (PAI-1) levels were measured using sandwich ELISA (R&D Systems, Minneapolis, MN). We classified the recruited obese asthmatic patients into two groups: patients with obese asthma with positive type-2 inflammation markers (S-T2, peripheral blood eosinophil counts ≥ 300/µL or a specific allergen detected) and patients with obese asthma with negative type-2 inflammation markers (S-NT2, peripheral blood eosinophil counts < 300/µL, and no specific allergen detected). Serum adipocytokines were compared between the groups. This study was approved by The Fraternity Memorial Hospital Research Ethics Committee and performed according to the Declaration of Helsinki. Written informed consent was obtained from all participating patients.
Statistical analysis
Data were compared using the Mann–Whitney U test. Fisher’s exact test was used to compare the proportions of categorical variables. In addition, multivariable logistic regression analysis was performed to identify factors independently associated with the T2 group. Statistical significance was set at p < 0.05. All statistical analyses were performed using the SPSS ver. 28 software (IBM, Armonk, NY).