Mild asthma: implications for the "MAPLE" longitudinal study, disease progression, exacerbations, triggers, phenotypes and endotypes.

Mild asthma accounts for 50-75% of cases yet carries a high burden of exacerbations, lung function decline, and corticosteroid exposure. The MAPLE study is a 5-year longitudinal study assessing phenotypes, endotypes and disease progression. Patients undergo annual assessments (spirometry, FOT, FeNO, ACQ, AIRQ, biospecimens), with interim at-home reporting. Patients assessed in clinics prior to being considered for enrolment into the MAPLE study provide useful cross-sectional data in which to investigate the importance of including milder asthma patients in longitudinal studies. Among 95 GINA1-3 patients with FOT data (median age 28, BMI 26, 41% female, 74% white Caucasian with no current smokers), 27% were GINA step 1, 24% step 2, 48% step 3, and 12% had poor control (ACQ-6≥1.5). Atopy was present in 99%, 85% sensitised to ≥2 allergens, 72%≥3, and 46%≥4. Using AIRQ, 2% were very poorly controlled (≥5), 24% were at least not well controlled (≥2), while 12% were poorly controlled by ACQ-6 (≥1.5). Small airway dysfunction (SAD) was present in 20-37% of patients and 13-30% of those with normal central airway function, associating with lower FEV₁ and FEV₁/FVC, greater bronchodilator response, higher eosinophils and worse control. T2-high (BEC≥300µL or FeNO≥50ppb,n=94) was found in 37%, associating with lower FEV₁/FVC, greater bronchodilator response, and higher HDM sensitisation. These cross-sectional findings highlight the prevalence of SAD and T2 inflammation in milder more controlled asthma. Including milder and more controlled patients in the MAPLE longitudinal study will give insights into disease progression, and stability of endotypes.