Background Lung clearance index (LCI) is a promising lung function outcome in individuals with primary ciliary dyskinesia (PCD). The impact of events clinically important for individuals with PCD, such as pulmonary exacerbations, on LCI is unknown.

Methods We conducted an international, multicentre, observational cohort study to assess the association of LCI and risk of pulmonary exacerbation, specific changes in LCI during pulmonary exacerbation and global variability of LCI across four visits every 4 months. Ninety individuals with PCD, aged 3–41 years, underwent nitrogen multiple-breath washout (MBW) and spirometry measurements. The association of LCI and pulmonary exacerbations was assessed by Cox proportional hazards and random-effects regression models.

Results We obtained 430 MBW and 427 spirometry measurements. In total, 379 person-years at risk contributed to the analysis. Per one unit increase (deterioration) in LCI, the risk of future pulmonary exacerbation increased by 13%: HR (95% CI), 1.13 (1.04 to 1.23). If LCI changed from a range of values considered normal to abnormal, the risk of future pulmonary exacerbations increased by 87%: 1.87 (1.08 to 3.23). During pulmonary exacerbations, LCI increased by 1.22 units (14.5%). After pulmonary exacerbations, LCI tended to decline. Estimates of variability in LCI suggested lower variation within individuals compared with variation between individuals. Findings were comparable for forced expiratory volume in 1 s.

Conclusion On a visit-to-visit basis, LCI measurement may add to the prediction of pulmonary exacerbations, the assessment of lung function decline and the potential lung function response to treatment of pulmonary exacerbations.