Dynein axonemal heavy chain 5 (DNAH5) is the most mutated gene in primary ciliary dyskinesia (PCD), leading to abnormal cilia ultrastructure and function. Few studies have revealed the genetic characteristics and pathogenetic mechanisms of PCD caused by DNAH5 mutation. Here, we established a child PCD airway organoid directly from the bronchoscopic biopsy of a patient with the DNAH5 mutation. The motile cilia in the organoid were observed and could be stably maintained for an extended time. We further found abnormal ciliary function and a decreased immune response caused by the DNAH5 mutation through single-cell RNA sequencing (scRNA-Seq) and proteomic analyses. Additionally, the directed induction of the ciliated cells, regulated by TGF-β/BMP and the Notch pathway, also increased the expression of inflammatory cytokines. Taken together, these results demonstrated that the combination of multiomics analysis and organoid modelling could reveal the close connection between the immune response and the DNAH5 gene.

Objective: This study explored the clinical features and immune responses of children with primary ciliary dyskinesia (PCD) during pneumonia episodes. Methods: The 61 children with PCD who were admitted to hospital because of pneumonia were retrospectively enrolled into this study between April 2017 and August 2022. A total of 61 children with pneumonia but without chronic diseases were enrolled as the control group. The clinical characteristics, levels of inflammatory indicators, pathogens, and imaging features of the lungs were compared between the two groups. Results: The PCD group had higher levels of lymphocytes (42.80% versus 36.00%, p = 0.029) and eosinophils (2.40% versus 1.25%, p = 0.020), but lower neutrophil counts (3.99 versus 5.75 × 10⁹/L, p = 0.011), percentages of neutrophils (46.39% versus 54.24%, p = 0.014), CRP (0.40 versus 4.20 mg/L, p < 0.001) and fibrinogen (257.50 versus 338.00 mg/dL, p = 0.010) levels. Children with PCD and children without chronic diseases were both most commonly infected with Mycoplasma pneumoniae (24.6% versus 51.9%). Children with PCD had significantly more common imaging features, including mucous plugging (p = 0.042), emphysema (p = 0.007), bronchiectasis (p < 0.001), mosaic attenuation (p = 0.012), interstitial inflammation (p = 0.015), and sinusitis (p < 0.001). Conclusion: PCD is linked to immune system impairment, which significantly contributes to our understanding of the pathophysiology of this entity.

Introduction: Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infections in infants and young children, and it constitutes a significant risk factor for the development of bronchiolitis and subsequent childhood asthma. The severity of the disease is notably higher in infants compared to adults, underscoring the urgent need for effective therapeutic interventions. Methods: In our study, we utilized pediatric nasal and airway epithelial organoids to demonstrate that both type I and type III interferons (IFNs) markedly reduce viral load and downregulate key inflammatory mediators, including IL-6, CXCL8, IL-1α, and TNF, during RSV infection. Through transcriptome Sequencing and multiplex cytokine profiling of 46 immune mediators, we observed a more robust immune response in the nasal epithelium compared to the airway epithelium. Results: Notably, IFN-λ1 was most effective in suppressing inflammation in the nasal epithelium, whereas IFN-β did not exacerbate inflammatory responses in the airway epithelium. Discussion: These findings provide novel insights for optimizing clinical IFN therapy, particularly in terms of selecting the appropriate interferon type, delivery site, and dosing strategy.

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.