Pulmonary exacerbations in patients with genetically confirmed PCD: a prospective observational multicentre study

Primary ciliary dyskinesia (PCD) is a rare genetic disorder characterized by deficient mucociliary clearance and development of chronic lung disease. Pulmonary exacerbations (PEx) in chronic lung diseases increase morbidity and lung function decline, but their frequency in PCD has been understudied. We aimed to prospectively determine the annual frequency of PEx in PCD and identify related risk factors.

In a multicentre, observational study conducted in 11 centres from seven countries, we prospectively collected data from a well-described patient cohort with genetically confirmed PCD over a year via monthly telephone questionnaires and clinical visits. We assessed the annual PEx frequency using three definitions: i) clinical definition 1 (Def-1) when three out of seven clinical items were positive; clinical definition 2 (Def-2) if the patient started or changed antibiotic treatment; self-reported PEx by the patient. For paired statistical comparisons we used the Friedman test and the Wilcoxon matched-pairs test and tested their agreement (Cohen's kappa statistics). We also determined related risk factors using a mixed-effects model.

We recruited 271 individuals with PCD of all ages. Among patients with complete annual records (n = 248), approximately 80% experienced at least one PEx per year, as assessed by the three definitions used. Self-reported PEx per year (median 2, interquartile range (IQR) 1-5) were higher (p < 0.0001) than the PEx assessed by Def-1 (median 2, IQR 0-4) and Def-2 (median 1, IQR 0.25-3). Self-reported PEx had a substantial agreement with Def-1 [kappa (SE) = 0.61 (0.05)] and a moderate agreement with Def-2 [kappa (SE) = 0.51 (0.05)]. Female sex and autumn season were associated with higher number of PEx, independent of the definition used. Increasing age was correlated with higher annual PEx frequency by Def-1.

In this multicentre study, we prospectively assessed the annual PEx frequency in patients genetically diagnosed with PCD, demonstrating the importance of the definition used in capturing the exacerbation burden of PCD, as well as the influence of sex, age and season on exacerbation frequency.