Longitudinal Lung Volume Changes by Ultrastructure and Genotype in Primary Ciliary Dyskinesia.

RATIONALE Genotype-phenotype relationships are emerging in primary ciliary dyskinesia (PCD), but little is known about lung volume changes over time. OBJECTIVES To investigate evolution of static lung volumes with ultrastructural defects, gene mutations, BMI, and specific infections in PCD. METHODS Prospective, longitudinal, single-center study in children and adults evaluated twice yearly for up to 10 years. Linear mixed effects models were used to assess associations between ciliary morphology, genetic mutations, and clinical features. RESULTS 122 patients had 1096 visits. At enrollment, almost all spirometric and, especially in adults, plethysmographic parameters were significantly worse in absent inner dynein arms, central apparatus defects, and microtubular disorganization (IDA/CA/MTD) compared with Normal Electron Microscopy (EM) patients. Mean trend increase with time for residual volume (RV) was significantly higher in IDA/CA/MTD compared to outer dynein arms (ODA) defect and Normal EM groups. Mean trend of RV/total lung capacity (TLC) in IDA/CA/MTD was significantly worse than in all other groups. The steepest rise in lung volumes was in CCDC39/CCDC40, while hyperinflation increased less in DNAH5 and DNAH11 groups. RV/TLC showed a significantly steeper rise in patients with Pseudomonas aeruginosa compared to other infections, or without infection. CONCLUSIONS Patients with IDA/CA/MTD defects or CCDC39/CCDC40 mutations had the greatest increase in hyperinflation, while those with ODA defect and Normal EM or DNAH11 and DNAH5 mutations had less severe changes. We have robustly confirmed the worse prognosis for some genetic and ultrastructural defects, which association hitherto rested solely on spirometry.