Metformin Treatment for Children With Obesity-associated Asthma

The primary outcome measure is the change in the Asthma Control Test (ACT) score after 26 weeks of intervention. The ACT is a validated questionnaire used to assess asthma control, including symptoms such as cough, wheezing, use of bronchodilators, nocturnal symptoms, shortness of breath, and limitations in daily activities.

For participants aged 12-17 years, the ACT score ranges from 0 to 25, where higher scores indicate better asthma control. Scores of 21-25 represent well-controlled asthma, 16-20 indicate poorly controlled asthma, and 0-15 indicate very poorly controlled asthma.

For participants aged 4-11 years, the Childhood Asthma Control Test (C-ACT) score ranges from 0 to 27, where higher scores also indicate better asthma control. Scores of 21-27 represent well-controlled asthma, 13-20 indicate poorly controlled asthma, and 0-12 indicate very poorly controlled asthma.

Changes in the annualized asthma exacerbation rate during the intervention period, assessed by the total number of asthma exacerbations experienced per participant per year; lower exacerbation rates indicate better asthma control and improved clinical outcomes.

Change in corticosteroid use during the intervention period, assessed by the frequency and/or dose of corticosteroid medication required by participants; reduced corticosteroid use indicates improved asthma control and better clinical outcomes.

Forced expiratory volume in 1 second (FEV1) after 26 weeks of intervention, assessed as percent predicted FEV1 measured by spirometry; higher percent predicted FEV1 values indicate better pulmonary function and improved asthma control.

Forced vital capacity (FVC) after 26 weeks of intervention, assessed as percent predicted FVC measured by spirometry; higher percent predicted FVC values indicate better lung function and improved respiratory capacity.

Pediatric Asthma Quality of Life Questionnaire (PAQLQ) scores after 26 weeks of intervention, assessed using the validated PAQLQ instrument; which measures both physical and emotional impact of asthma. The questionnaire has three domains including asthma symptoms (6 items), emotional function (4 items) and activity limitation (3 items), scale ranging from 1 to 7, where higher scores indicate better quality of life and improved symptom control.

Change in body mass index (BMI) after 26 weeks of intervention, assessed as weight in kilograms divided by height in meters squared (kg/m²); lower BMI values or improvement toward age-appropriate BMI ranges indicate better weight management outcomes.

Peripheral blood eosinophil count after 26 weeks of intervention, assessed as the absolute eosinophil count in peripheral blood (cells/µL). Lower eosinophil counts may indicate reduced type 2 inflammation and improved asthma control following the intervention.

Fasting plasma glucose after 26 weeks of intervention, assessed by measuring fasting blood glucose concentration in plasma (mmol/L); lower values within the normal reference range indicate improved glycemic control and metabolic status.

Fasting insulin levels after 26 weeks of intervention, assessed by measuring fasting serum insulin concentration (pmol/L); lower fasting insulin levels within the normal reference range indicate improved insulin sensitivity and metabolic control.

Changes in the levels of plasma cytokines including IL-22, IFN-γ, TNF-α, IL-2, IL-4, IL-5, IL-10, IL-13, IL-17A, IL-33, and leptin will be measured (pg/mL) after 26 weeks of intervention to evaluate the effect of the treatment on systemic inflammatory responses.

Plasma metabolomic and lipidomic profiles will be measured as relative concentrations of metabolites and lipids (normalized intensity units) after 26 weeks of intervention to assess changes associated with the treatment.

Blood transcriptomic profile will be measured as normalized fold-change values in gene expression after 26 weeks of intervention to assess transcriptomic changes associated with the treatment.

Gut and salivary microbiome profiles will be measured as the relative abundance (%) and diversity indices of microbial taxa at the phylum, genus, and species levels after 26 weeks of intervention.