How to define the LLN in spirometry: associations of different percentile thresholds with respiratory symptoms and mortality

<bold>Background:</bold> Traditionally, the lower limit of normal (LLN) in spirometry has been set at the 5th percentile, but the latest ERS/ATS guidelines on lung function tests interpretation suggest that the choice of the threshold should be anchored to relevant clinical outcomes. <bold>Methods:</bold> In 26,091 30–46 years old men, who participated in a general population survey in Norway in 1988–90, we studied the associations between baseline spirometric abnormalities (FEV1<LLN, FVC<LLN, airflow obstruction, spirometric restriction) defined with different LLN thresholds (5th, 2.5th, 1st percentile) and prevalence of spirometric abnormalities, respiratory symptoms, and mortality after 26 years. Analyses were performed with local and GLI-2012 reference equations and adjusted for age, BMI, smoking, education. <bold>Results:</bold> The prevalence of airflow obstruction was 11.0% with local-LLN5, 6.1% with GLI-LLN5, 7.6% with local-LLN2.5, and 3.5% with GLI-LLN2.5. Spirometric abnormalities defined with increasingly lower LLN thresholds were associated with increased ORs of respiratory symptoms using both local and GLI equations, but ORs for the same threshold were higher for GLI compared to local. HRs of mortality for spirometric abnormalities defined with local-LLN2.5 in asymptomatic subjects (1.28–1.51) were comparable to those defined with local-LLN5 in the total population (1.45–1.71) and symptomatic subjects (1.47–1.69). Similar HRs were observed with GLI-LLN5 and GLI-LLN10. <bold>Conclusions:</bold> In spirometry, a lower LLN threshold might be used in asymptomatic subjects, and a higher threshold in symptomatic subjects, but the choice of the threshold is related to the choice of reference equations.