Primary Ciliary Dyskinesia Due to Microtubular Defects is Associated with Worse Lung Clearance Index

PURPOSE: Primary ciliary dyskinesia (PCD) is characterised by repeated upper and lower respiratory tract infections, neutrophilic airway inflammation and obstructive airway disease. Different ultrastructural ciliary defects may affect lung function decline to different degrees. Lung clearance index (LCI) is a marker of ventilation inhomogeneity that is raised in some but not all patients with PCD. We hypothesised that PCD patients with microtubular defects would have worse (higher) LCI than other PCD patients. METHODS: Spirometry and LCI were measured in 69 stable patients with PCD. Age at testing, age at diagnosis, ethnicity, ciliary ultrastructure, genetic screening result and any growth of Pseudomonas aeruginosa was recorded. RESULTS: Lung clearance index was more abnormal in PCD patients with microtubular defects (median 10.24) than those with dynein arm defects (median 8.3, p = 0.004) or normal ultrastructure (median 7.63, p = 0.0004). Age is correlated with LCI, with older patients having worse LCI values (p = 0.03, r = 0.3). CONCLUSION: This study shows that cilia microtubular defects are associated with worse LCI in PCD than dynein arm defects or normal ultrastructure. The patient's age at testing is also associated with a higher LCI. Patients at greater risk of obstructive lung disease should be considered for more aggressive management. Differences between patient groups may potentially open avenues for novel treatments

International Consensus Statement on Rhinology and Allergy: Rhinosinusitis

Background: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR‐RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR‐RS‐2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence‐based findings of the document. Methods: ICAR‐RS presents over 180 topics in the forms of evidence‐based reviews with recommendations (EBRRs), evidence‐based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. Results: ICAR‐RS‐2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence‐based management algorithm is provided. Conclusion: This ICAR‐RS‐2021 executive summary provides a compilation of the evidence‐based recommendations for medical and surgical treatment of the most common forms of RS

A longitudinal study of lung bacterial pathogens in patients with primary ciliary dyskinesia

AbstractIn patients with primary ciliary dyskinesia (PCD), impaired mucociliary clearance leads to an accumulation of secretions in the airways and susceptibility to repeated bacterial infections. The primary aim of this study was to investigate the bacterial flora in non-chronic and chronic infections in the lower airways of patients with PCD. We retrospectively reviewed the presence of bacteria from patients with PCD during an 11-year period and genotyped 35 Pseudomonas aeruginosa isolates from 12 patients with chronic infection using pulsed-field gel electrophoresis. We identified 5450 evaluable cultures from 107 patients with PCD (median age 17 years, range 0–74 years) (median age at diagnosis 7.8 years, range 0–63 years). Haemophilus influenzae was the most frequent microorganism. Other common pathogens were P. aeruginosa, Streptococcus pneumoniae, Moraxella catarrhalis and Staphylococcus aureus. The number of patients colonized with P. aeruginosa at least once varied from 11 to 44 patients (15–47%) annually, and 42 patients (39%) met the criteria for chronic infection at least once. Pseudomonas aeruginosa was more frequently isolated in teenagers and adults than children (p 0.02) and the prevalence was significantly lower in patients with preschool (<6 years) PCD diagnosis (p 0.04). Ten out of 12 patients (83%) were chronically infected with a unique clone-type of P. aeruginosa. No sharing of clone-types or patient-to-patient transmission was observed. In conclusion, PCD patients were infected by a unique set of bacteria acquired in an age-dependent sequence. Pseudomonas aeruginosa frequently colonizes the lower respiratory tract and the incidence of chronic infection was higher than previously reported

The Role of Psychiatrists in Consultation-Liaison Psychiatry

Infections with Pseudomonas aeruginosa increase morbidity in primary ciliary dyskinesia (PCD) and cystic fibrosis (CF) patients. Both diseases are associated with a defect of the mucociliary clearance; in PCD caused by non-functional cilia, in CF by changed mucus. Whole genome sequencing of P. aeruginosa isolates from CF patients has shown that persistence of clonal lineages in the airways is facilitated by genetic adaptation. It is unknown whether this also applies to P. aeruginosa airway infections in PCD. We compared within-host evolution of P. aeruginosa in PCD and CF patients. P. aeruginosa isolates from 12 PCD patients were whole genome sequenced and phenotypically characterised. Ten out of 12 PCD patients were infected with persisting clone types. We identified convergent evolution in eight genes, which are also important for persistent infections in CF airways: genes related to antibiotic resistance, quorum sensing, motility, type III secretion and mucoidity. We document phenotypic and genotypic parallelism in the evolution of P. aeruginosa across infected patients with different genetic disorders. The parallel changes and convergent adaptation and evolution may be caused by similar selective forces such as the intensive antibiotic treatment and the inflammatory response, which drive the evolutionary processes