線毛機能不全症候群（カルタゲナー症候群を含む。）

Primary ciliary dyskinesia (PCD) is an inherited motile-cilia disorder. Impaired mucociliary transport promotes persistent secretion retention, infection, inflammation, and bronchiectasis. The central treatment problem is therefore failure of airway clearance rather than infection alone. This narrative review evaluates airway clearance techniques (ACTs), mucoactive adjuncts, and pulmonary rehabilitation for children and adolescents. We prioritize direct pediatric PCD evidence, identify mixed-age or adult PCD findings as population-bound PCD evidence, and label pediatric bronchiectasis and cystic fibrosis evidence as indirect. Because no ACT has been shown to be universally superior and pediatric rehabilitation evidence remains limited, we present an author-proposed clearance-anchored dual-pillar framework. ACTs directly address mucus retention. Pulmonary rehabilitation complements ACT by targeting fitness, muscle performance, participation, and self-management. Response should be assessed across four domains: clinical stability, treatment performance, physiological and functional outcomes, and patient and family experience. Prospective multicenter comparative trials and harmonized pediatric outcome measures are urgently needed.

The ciliary transition zone (TZ) regulates ciliary proteome composition, yet its molecular architecture, protein content, and contribution to motile ciliopathies remain poorly defined. We applied in situ cryo-electron tomography and subtomogram averaging to human multiciliated epithelial cells. This approach resolved TZ-specific doublet microtubules at subnanometer resolution and identified nine constituent proteins. We identified that ECT2L and DZANK1 form the major linker complexes between adjacent TZ doublet microtubules. Biallelic loss-of-function variants in either gene cause primary ciliary dyskinesia. ECT2L and DZANK1 deficiency disrupted TZ architecture, caused microtubular abnormalities and abnormal bulbous ciliary tips, and impaired mucociliary clearance. These findings establish a direct genetic link between TZ defects and human motile ciliopathy, and illustrate how in situ structural biology can uncover mechanisms of human disease.

Chronic airway diseases such as cystic fibrosis (CF) and primary ciliary dyskinesia (PCD) pose substantial clinical challenges. Here, we explore the p.C97W variant in WAP four-disulfide core domain protein 2 (WFDC2), proposed as a new genetic origin of respiratory distress, especially among Koreans. Whole-exome and whole-genome sequencing (WES/WGS) are performed on 64 patients from 62 families presenting with severe bronchiectasis and chronic rhinosinusitis. Pathogenic variants are found in 19.4% of families, including a novel homozygous WFDC2 missense variant (c.291 C > G, p.Cys97Trp) in five unrelated families. WFDC2 is expressed in lung epithelial cells, and the p.C97W variant impairs WFDC2 protein folding, secretion, and function. Wfdc2 p.C147W knock-in mice exhibit respiratory failure due to the hyperactive epithelial sodium channel (ENaC) linked to increased PRSS8 activity and recapitulate human disease. Treatment with amiloride, an ENaC inhibitor, improves survival and respiratory function in these mice. In conclusion, the p.C97W variant in WFDC2 is a critical genetic factor in severe chronic airway disease that shares clinical features with CF and PCD. Given its implications for diagnosis and treatment, genetic testing for WFDC2 mutations in individuals with CF- or PCD-like symptoms is recommended.

UNLABELLED: Primary ciliary dyskinesia (PCD) is a rare inherited disorder of motile ciliary dysfunction characterized by impaired mucociliary clearance, chronic sino-pulmonary disease, and progressive bronchiectasis. Pulmonary exacerbations (PEx) are a major contributor to morbidity, lung function decline, and healthcare utilization in PCD, yet historically have been poorly defined and understudied. This review summarizes current evidence regarding the definition, epidemiology, pathophysiology, clinical impact, and management of PEx in PCD, with emphasis on recent advances that are beginning to establish a disease-specific evidence base. Recent international consensus efforts have proposed standardized definitions for PEx, although significant heterogeneity remains across clinical studies. Prospective cohort data demonstrate that PEx occur frequently across all age groups, including infancy, and are associated with impaired lung function recovery, structural lung damage, and increased disease severity, particularly in patients with chronic Pseudomonas aeruginosa infection. Emerging biomarkers such as lung clearance index and exhaled breath analysis using volatile organic compounds may improve prediction and monitoring of exacerbations. Management strategies currently rely largely on extrapolation from cystic fibrosis and non-cystic fibrosis bronchiectasis and include prompt antibiotic therapy, intensified airway clearance, and supportive care. However, recent randomized controlled trials, including BESTCILIA and CLEAN-PCD, have provided the first high-quality evidence supporting maintenance azithromycin therapy and airway hydration strategies in PCD. Despite these advances, important gaps remain regarding optimal exacerbation definitions, treatment duration, predictors of incomplete recovery, and the role of anti-inflammatory and targeted therapies. CONCLUSION: Continued international collaboration, validated outcome measures, and development of mechanism-based therapies will be essential to improve long-term outcomes for patients with PCD. WHAT IS KNOWN: • Primary ciliary dyskinesia (PCD) is a rare inherited disorder of motile ciliary dysfunction causing chronic sino-pulmonary disease, recurrent respiratory infections, and progressive bronchiectasis from early childhood. • Pulmonary exacerbations (PEx) are a major driver of morbidity and lung function decline in PCD, but have historically been inconsistently defined and understudied, with management largely extrapolated from cystic fibrosis and non-CF bronchiectasis. Recent international consensus efforts have proposed standardized definitions for PEx, although significant heterogeneity remains across clinical studies. WHAT IS NEW: • Prospective international cohort data (Schreck et al. 2026) establish a PEx incidence of approximately 3.1 per person per year across all age groups, with higher risk in adult females and Pseudomonas aeruginosa-colonized patients. PEx are frequent even in the first 2 years of life. Pulmonary exacerbations cause substantial acute loss in forced expiratory volume in 1 s (FEV1), and approximately 20-25% of events do not recover to baseline lung function. • The BESTCILIA trial provides the first high-quality evidence that maintenance azithromycin reduces PEx frequency by 55% in PCD, and the CLEAN-PCD trial provides proof-of-concept for airway rehydration (ENaC blockade + hypertonic saline) as a PCD-specific therapeutic strategy.Novel anti-inflammatory therapies (DPP1 inhibitors, neutrophil elastase inhibitors), inhaled biologics, and gene-directed strategies are entering the PCD therapeutic pipeline and may transform future PEx prevention.

INTRODUCTION: Primary ciliary dyskinesia (PCD) is a rare disorder of impaired respiratory mucociliary clearance and chronic pulmonary infections. The clinical impact of chronic infection is poorly understood. The objective of this single-center, retrospective cohort study was to assess clinical outcomes of people with PCD and chronic airway infection. We hypothesized that chronic airway infection would be associated with greater declines in lung function and higher pulmonary exacerbation rates. METHODS: Linear mixed effects models were used to analyze the association of chronic infection with percent predicted forced expiratory volume in 1 s (ppFEV1). Poisson mixed models were used to analyze the association of chronic infection with exacerbation rates. RESULTS: Thirty-two people with PCD were included: 19 (59%) with chronic infection including 5 (16%) with chronic Pseudomonas aeruginosa (PA), 10 (31%) with chronic Haemophilus influenzae (HI), 2 (6%) with chronic methicillin-sensitive Staphylococcus aureus (MSSA) and 2 (6%) with chronic Aspergillus fumigatus (AF). A lower ppFEV1 was associated with chronic AF, but not with other chronic infections. The exacerbation rate ratio was 1.29 [95% CI 0.72, 2.30] (p = 0.388), 5.03 [95% CI 1.41, 18.0] (p = 0.013), 0.41 [95% CI 0.16, 1.08] (p = 0.072) and 2.19 [95% CI 0.39, 12.30] (p = 0.373) after development of chronic HI infection, chronic PA infection, chronic MSSA infection and chronic AF infection, respectively. CONCLUSION: In this single-center, retrospective study of chronic airway infections in PCD, chronic infection with PA was associated with a greater rate of pulmonary exacerbations but ppFEV1 decline was only associated with chronic AF infection.