線毛機能不全症候群（カルタゲナー症候群を含む。）

INTRODUCTION: Primary Ciliary Dyskinesia (PCD) is a rare genetic disorder caused by defective ciliary structure and function, leading to chronic respiratory and systemic manifestations. Diagnostic pathways have evolved over time, but no single standalone test exists. METHODS: Retrospective study of PCD patients followed at a Portuguese tertiary hospital, between 2001-2024. RESULTS: Thirty-five patients with a confirmed diagnosis were included: 13 children and 22 adults. Median age at diagnosis was 7 years (0-16) in children and 38.5 years (12-64) in adults. Time to diagnosis decreased over the years, coinciding with a shift in the hierarchy of methods from high-speed video microscopy and transmission electron microscopy to genetic testing. The most frequent mutations were DNAH5 (31.3%) and DNAH11 (12.5%). Pulmonary function tended to be better in children (p = 0.085), whereas bronchiectasis were more extensive and bilateral in adults (p = 0.044 and p = 0.002, respectively). Children more frequently received treatment with hypertonic saline (p = 0.003) and adults with bronchodilators (p = 0.035). Pseudomonas aeruginosa was only identified in adults; inhaled antibiotics were only prescribed in this age group (18.2%). CONCLUSION: This represents the largest Portuguese cohort to date and provides relevant clinical and diagnostic insight into age-related differences, supporting the importance of early detection and intervention to limit lung damage.

BACKGROUND: Primary ciliary dyskinesia (PCD) is a rare genetic disorder that is predominantly inherited in an autosomal recessive pattern and is caused by structural or functional ciliary abnormalities. Previous studies on the genetic susceptibility prevalence of PCD have been largely based on limited populations, and there is a lack of global estimates derived from large-scale population genetic databases. This study estimates the carrier frequency and genetic susceptibility prevalence of PCD via the latest data from the gnomAD v4.1.0 database and compares the results with those of previous studies. METHODS: We selected genes related to PCD with "Definitive" or "Strong" associations as determined by the ClinGen Motile Ciliopathy Gene Curation Expert Panel. According to ACMG/AMP guidelines, variables were classified for pathogenicity, including loss-of-function variants (pLOFs) and pathogenic/likely pathogenic missense variants. Using the allele frequency (AF) of these variants from the Genome Aggregation Database (gnomAD) v4.1.0 (containing data from 807,162 individuals) and applying the Hardy‒Weinberg equilibrium principle, we calculated the global and population-specific genetic susceptibility prevalence and carrier frequency of PCD. RESULTS: Among the 31 PCD-associated genes, 5252 eligible variants were included, comprising 5156 pLOF and 96 P/LP variants. The estimated global genetic susceptibility prevalence of PCD is approximately 1 in 20,103, with a corresponding overall carrier frequency of approximately 1 in 25. The Middle East region has the highest prevalence rate of 1 in 4,744, as well as the highest carrier frequency. CONCLUSION: The estimated global genetic susceptibility prevalence of primary ciliary dyskinesia is approximately 1 in 20,103, with an overall carrier frequency of 1 in 25, indicating significant heterogeneity among ethnic populations. The global genetic susceptibility prevalence estimate is lower than the previous estimate of 1/7,554.

BACKGROUND: End user co-design in the personal digital health technology space is underdeveloped. Clinical uptake of personal digital health technologies has been poor, highlighting a need to cocreate solutions with end users. OBJECTIVE: The study aimed to describe an "end user" co-design framework in the development of 5 prototype personal health apps for patients with different rare or complex diseases. METHODS: A patient-led, user-centered, collaborative personal health app plus wearable plug-in co-design methodology was developed. Five prototype apps were developed for end users with long COVID-19, pancreatitis, primary ciliary dyskinesia, sarcoidosis, and valosin-containing protein disease by a multidisciplinary partnership including patients, app design and development experts, user experience experts, clinicians, and patient-driven organizations. Phase 1 involved a 6-month co-design process with 5 modules involving patient-driven organizations that included the codevelopment of specifications through group workshops and independent exercises that defined the goals, content, features, and user experience of each app. Phase 2 involved app build-out, internal alpha testing, and beta study preparations. Phase 3 involved a usability beta testing study in which end users used the app and associated wearable/smart devices (Oura ring, Lumia ear device, Empatica EmbracePlus, and MIR Spirobank Spirometer) for up to 5 months. Participant feedback was documented continuously and systematically, centering on the following themes: functionality, usability, harms, benefits, self-explorations, and beta testing study details related to retention and adherence. RESULTS: While unique app goals were codeveloped by each disease group, a central goal across groups was to develop a personal health app enabling users to track subjective, self-reported symptoms, objective measures of health, and unique modifiers of symptoms. A total of 239 end user participants participated in the beta testing pilot study. Enrollment and retention rates were high, ranging from 94% to 100% and 92.2% to 100%, respectively. All active participants gave some form of feedback: there were 257 unique participant suggestions of how to specifically modify or improve the study app experience. Participant feedback themes commonly centered around customization to reduce daily burden and improve personal tailoring of the app. Participants' desires surrounding symptom displays were heterogeneous. CONCLUSIONS: Personal health app co-design is rooted in a complex digital landscape that requires a significant amount of up-front effort and time. However, the up-front investment of time can result in rich and diverse end user feedback that could save time in the app development trajectory to implementation. This paper provides a co-design framework and the building blocks of 5 prototype personal health apps with publicly available open-source code on GitHub. These prototypes could be leveraged for improving understanding of, communicating symptoms of, and providing n-of-1 suggestions for rare or complex diseases, providing benefit to patient communities and individual patients.

BACKGROUND: Airway clearance techniques (ACTs) are required in international bronchiectasis (BE) management guidelines, and high frequency chest wall oscillation (HFCWO) is the only ACT with a Centers for Medicare and Medicaid Services (CMS) reimbursement guideline. OBJECTIVE: Compare patient demographics and clinical characteristics between BE patients using HFCWO to BE patients not using HFCWO. METHODS: Bronchiectasis and Nontuberculous Mycobacteria Research Registry (BRR) (2008-2025) data were retrospectively analyzed. Patients were grouped by baseline HFCWO use and non-users were further stratified by selected CMS eligibility criteria (productive cough or more than two exacerbations per year) and subsequent HFCWO utilization. RESULTS: Of 5,673 patients (median age 69 years), 518 used HFCWO and 5,155 did not. HFCWO users had higher rates of asthma (31.7 vs. 25.3%, P=0.002), gastroesophageal reflux disease (48.5 vs. 41.9%, P=0.004), primary ciliary dyskinesia (5.8 vs. 2.1%, P<0.001), allergic bronchopulmonary aspergillosis (3.3 vs. 1.7%, P=0.013) and nontuberculous mycobacteria (20.1 vs. 15.7%, P=0.011). Symptoms more common in HFCWO users included dyspnea (72.1 vs. 38.5%), fatigue (61.5 vs. 46.8%), cough (90.9 vs. 76.6%,), and hemoptysis (27.1 vs 19.8%) (all P<0.001). Median modified bronchiectasis severity index (mBSI) score was higher in HFCWO users (8 vs. 7, P<0.001), and HFCWO users more frequently received antibiotics, bronchodilators, hypertonic saline, inhaled and oral corticosteroids, indicating greater disease burden. Notably, 58% (2,703/4,679) of non-HFCWO users appeared to meet selected CMS symptom/exacerbation criteria and their characteristics resembled HFCWO users. CONCLUSION: These findings suggest areas to explore to standardize BE management and motivate clearer treatment guidelines to optimize patient health outcomes.

We report the case of a young woman with primary ciliary dyskinesia (PCD) who was also diagnosed with tRNA nucleotidyl transferase 1 (TRNT1)-related autoinflammatory syndrome, characterized by recurrent episodes of fever and arthralgia beginning at age 16. To our knowledge, this is the first documented case of homozygosity for the c.1246A>G variant in the TRNT1 gene. The patient had a milder clinical phenotype than previously reported cases with the same variant in a compound heterozygous state. Etanercept administration effectively controlled autoinflammatory manifestations, consistent with prior literature, and no adverse safety events were observed, despite the elevated risk of infectious pulmonary complications due to concurrent PCD. This case underscores the importance of considering autoinflammatory disease in patients presenting with relevant clinical features, even when manifestations are mild or have a delayed onset.