However, in a large cohort study (the COPD History Assessment in Spain (CHAIN) study), the diagnostic criteria required for ACO was one major criterion (bronchodilator test >400 mL and 15% and past medical history of asthma) or two minor criteria (blood eosinophils > 5%, IgE > 100 IU/mL, or two separate bronchodilator tests > 200 mL and 12%) [8]. This evidence concerns the gene IGHE and chronic obstructive pulmonary disease.