Abstract Rationale Patients with asthma are at risk for structural airway changes that contribute to accelerated loss of lung function. Identifying predictors of rapid lung function decline (LFD) can guide early intervention and monitoring. This study examined demographic, clinical, and type-2 inflammatory predictors of rapid LFD (100 mL/year). Methods We analyzed individual patient data from adult (≥18 years) asthma patients from control and placebo arms of randomized controlled trials in the OxfoRd Asthma attaCk risk scaLE (ORACLE2) meta-analysis. We selected patients with complete treatment step data, ≥12 weeks of follow-up (maximum 52 weeks) and ≥2 post-bronchodilator FEV₁ measurements. Data before week 12 were excluded to minimize placebo-response effects. Missing baseline data were imputed using multilevel multiple imputation. Annualized LFD was defined as the change in FEV₁ between the first and last measurement from week 12, standardized to mL/year. Rapid and extremely rapid LFD were defined as 100mL/year and 200 mL/year, respectively. Multivariable logistic regression models identified predictors of rapid and extremely rapid LFD, adjusting for potential confounders including age, sex, BMI, treatment step, attack history, smoking history, FEV1% reversibility, ACQ-5, trial, and type-2 biomarkers fractional exhaled nitric oxide (FeNO) and blood eosinophil count (BEC). Results A total of 1268 patients from five trials (BENRAP2B, LAVOLTA 1 and 2, Novel START, PRACTICAL) were included; 61% were female, mean (SD) age was 47(14) years, and 63% had moderate-to-severe asthma (steps 3-5). Median (IQR) follow-up was 365 (364-366) days. Rapid and extremely rapid LFD occurred in 42% and 31% of patients, respectively. In the multivariable analyses adjusted for potential confounders, younger age was associated with higher odds of extremely rapid LFD (OR 95%CI: 1.15 1.05-1.25 per 10 year decrease), but not with rapid LFD. Male sex was associated with higher odds of rapid (OR 95%CI: 1.39 1.10-1.76 vs. female) and extremely rapid LFD (1.61 1.26-2.06). Higher FeNO, but not BEC, showed a trend toward extremely rapid LFD (OR 95%CI: 1.40 0.95-2.07 per 10-fold increase). FeNO nor BEC were associated with rapid LFD (Figure 1). Conclusion Male sex and younger age independently predicted LFD in adults with asthma. Higher FeNO showed a trend toward extremely rapid decline. Findings from this large, harmonized dataset support early risk stratification and underscore the need for longer-term studies to validate predictors of LFD. Figure 1. Forest plot of associations between baseline predictors and rapid (100mL/year) and extremely rapid (200mL/year) lung function decline This abstract is funded by: APQ; FRQS; AIRS; AcMedSci; NIHR
Meulmeester et al. (Fri,) studied this question.