Neonatal diagnosis of primary ciliary dyskinesia in a high consanguinity population: a single tertiary center experience.

Though PCD usually presents after birth in term neonates, diagnosing PCD during the neonatal and infancy stages is uncommon, particularly in children who do not exhibit laterality defects. We report our recent experience with the diagnosis of PCD in the neonatal and early infantile period in a highly consanguine population. This was achieved by implementing a novel genetic-based diagnostic approach based on direct testing for recognized regional genetic variants. We conducted a retrospective analysis of children diagnosed with PCD at Soroka University Medical Center during the neonatal or early infantile period between 2020 and 2023. We included children under 3 months of age who had a genetic confirmation of PCD, as evidenced by the presence of two pathogenic variants in recognized genes. Genetic testing targeted regional genetic variants in previously identified PCD genes. Eight patients were included. The median age at diagnosis was 12.5 days. Three (38%) were born prematurely < 34 weeks gestational age. All patients were presented with respiratory distress and hypoxemia after birth. The median duration of oxygen support was 23 days, and upper lobe atelectasis was present in five patients (63%). Congenital cardiac malformation was present in four patients. Organ laterality defects were present in four patients. Genetic mutations identified were in the DNAAF5, DNAL1, DNAAF3, and DNAH1 genes.     Conclusion: Neonatal diagnosis of PCD is uncommon, especially in atypical presentations such as children without laterality defects or preterms. Focusing on a genetic diagnosis of the local tribal pathogenic variants promotes a potential cost-efficient test leading to earlier diagnosis. There is a need for a standardized protocol for earlier diagnosis of PCD in high-consanguinity areas. What is Known: • Primary ciliary dyskinesia (PCD) typically presents after birth in term neonates. • Diagnosing PCD during neonatal and infancy stages is challenging, particularly in children without laterality defects. What is New: • A novel genetic-based diagnostic approach was implemented on the neonatal population in a highly consanguine community, focusing on direct testing for regional genetic variants, leading to early and rapid diagnosis of PCD.

Genetic Spectrum and Clinical Characteristics of Patients with Primary Ciliary Dyskinesia: a Belgian Single Center Study.

PURPOSE: We aimed to examine the correlation between clinical characteristics and the pathogenic gene variants in patients with Primary Ciliary Dyskinesia (PCD). METHODS: We conducted a retrospective single-center study in patients with PCD followed at the University Hospitals Leuven. We included patients with genetically confirmed PCD and described their genotype, data from ultrastructural ciliary evaluation and clinical characteristics. Genotype/phenotype correlations were studied in patients with the most frequently involved genes. RESULTS: We enrolled 74 patients with a median age of 25.58 years. The most frequently involved genes were DNAH11 (n = 23) and DNAH5 (n = 19). The most frequent types of pathogenic variants were missense (n = 42) and frameshift variants (n = 36) and most patients had compound heterozygous variants (n = 44). Ciliary ultrastructure (p < 0.001), situs (p = 0.015) and age at diagnosis (median 9.50 vs 4.71 years, p = 0.037) differed between DNAH11 and DNAH5. When correcting for situs this difference in age at diagnosis was no longer significant (p = 0.973). Patients with situs inversus were diagnosed earlier (p = 0.031). Respiratory tract microbiology (p = 0.161), lung function (cross-sectional, p = 0.829 and longitudinal, p = 0.329) and chest CT abnormalities (p = 0.202) were not significantly different between DNAH11 and DNAH5 variants. CONCLUSION: This study suggests a genotype-phenotype correlation for some of the evaluated clinical characteristics of the two most frequently involved genes in this study, namely DNAH11 and DNAH5.

Situs Inversus Totalis in a Newborn With Primary Ciliary Dyskinesia.

Respiratory distress in the newborn is associated with numerous etiologies, some common and some rare. When respiratory distress is accompanied by laterality defects, namely, situs inversus (SI), the index of suspicion for comorbid primary ciliary dyskinesia (PCD) should be raised. Primary ciliary dyskinesia is characterized by ciliary dysmotility and the accumulation of thick secretions in the airways that obstruct air and gas exchange. Neonatal clinicians should know that while PCD is definitively diagnosed in infancy or early childhood, findings suspicious for PCD should be communicated to primary care providers at discharge from the hospital to facilitate timely subspecialty involvement, diagnosis, and treatment. This article will present a case report of a term newborn with SI totalis who was later diagnosed with PCD. We will discuss epidemiology, pathophysiology, clinical manifestations, and diagnostics, followed by management strategies. Additionally, we discuss the outpatient needs and lifespan implications.

Nasal nitric oxide measurement in children for the diagnosis of primary ciliary dyskinesia: European Respiratory Society technical standard.

Nasal nitric oxide (nNO) is extremely low in most people with primary ciliary dyskinesia (PCD) and its measurement is an important contributor to making the diagnosis. Existing guidelines and technical standards focus on nNO measurements in older, cooperative children using chemiluminescence analysers. However, measurements of nNO in pre-school-age children (age 2-5 years) may facilitate early diagnosis and electrochemical rather than chemiluminescence analysers are widely used. Pre-schoolers often need different methods to be employed when measuring nNO. Hence, a European Respiratory Society Task Force has developed this technical standard as the first step towards standardising sampling, analysis and reporting of nNO measured as part of the diagnostic testing for PCD in all age groups, including pre-school-age children. Furthermore, we considered both chemiluminescence and electrochemical analysers that are in use worldwide. There was a paucity of quality evidence for electrochemical analysers and sampling methods used in young children, and the Task Force proposes future research priorities to allow updates of this technical standard.

The RSPH4A Gene in Primary Ciliary Dyskinesia.

The radial spoke head protein 4 homolog A (RSPH4A) gene is one of more than 50 genes that cause Primary ciliary dyskinesia (PCD), a rare genetic ciliopathy. Genetic mutations in the RSPH4A gene alter an important protein structure involved in ciliary pathogenesis. Radial spoke proteins, such as RSPH4A, have been conserved across multiple species. In humans, ciliary function deficiency caused by RSPH4A pathogenic variants results in a clinical phenotype characterized by recurrent oto-sino-pulmonary infections. More than 30 pathogenic RSPH4A genetic variants have been associated with PCD. In Puerto Rican Hispanics, a founder mutation (RSPH4A (c.921+3_921+6delAAGT (intronic)) has been described. The spectrum of the RSPH4A PCD phenotype does not include laterality defects, which results in a challenging diagnosis. PCD diagnostic tools can combine transmission electron microscopy (TEM), nasal nitric oxide (nNO), High-Speed Video microscopy Analysis (HSVA), and immunofluorescence. The purpose of this review article is to provide a comprehensive overview of current knowledge about the RSPH4A gene in PCD, ranging from basic science to human clinical phenotype.

Un cas de situs inversus complet associé à une communication interventriculaire et des anomalies oculaires chez une chienne croisée de 3 ans.

A case of complete situs inversus associated with an interventricular communication and ocular abnormalities in a 3-year-old mixed-breed female dog. A 3-year-old female dog was referred for exploration of a murmur concomitant with lethargy. An echocardiogram reveals an inversion of the position of the cardiac chambers and the presence of an interventricular communication. A computed tomography examination of the thorax and abdomen highlights the known cardiac abnormalities as well as the association of a complete situs inversus. The clinical examination also reveals ocular malformations (deviation of the eyeballs and asymmetry of the fundus). This article highlights the variety of abnormalities that can be associated with the complete inversion of the organs and demonstrates that there may be variants to the more classic picture usually encountered in humans (respiratory manifestations related to Kartagener syndrome).(Translated by Dr Serge Messier).

Genome sequencing reveals underdiagnosis of primary ciliary dyskinesia in bronchiectasis.

BACKGROUND: Bronchiectasis can result from infectious, genetic, immunological and allergic causes. 60-80% of cases are idiopathic, but a well-recognised genetic cause is the motile ciliopathy, primary ciliary dyskinesia (PCD). Diagnosis of PCD has management implications including addressing comorbidities, implementing genetic and fertility counselling and future access to PCD-specific treatments. Diagnostic testing can be complex; however, PCD genetic testing is moving rapidly from research into clinical diagnostics and would confirm the cause of bronchiectasis. METHODS: This observational study used genetic data from severe bronchiectasis patients recruited to the UK 100,000 Genomes Project and patients referred for gene panel testing within a tertiary respiratory hospital. Patients referred for genetic testing due to clinical suspicion of PCD were excluded from both analyses. Data were accessed from the British Thoracic Society audit, to investigate whether motile ciliopathies are underdiagnosed in people with bronchiectasis in the UK. RESULTS: Pathogenic or likely pathogenic variants were identified in motile ciliopathy genes in 17 (12%) out of 142 individuals by whole-genome sequencing. Similarly, in a single centre with access to pathological diagnostic facilities, 5-10% of patients received a PCD diagnosis by gene panel, often linked to normal/inconclusive nasal nitric oxide and cilia functional test results. In 4898 audited patients with bronchiectasis, <2% were tested for PCD and <1% received genetic testing. CONCLUSIONS: PCD is underdiagnosed as a cause of bronchiectasis. Increased uptake of genetic testing may help to identify bronchiectasis due to motile ciliopathies and ensure appropriate management.

Combining RSPH9 founder mutation screening and next-generation sequencing analysis is efficient for primary ciliary dyskinesia diagnosis in Saudi patients.

Primary ciliary dyskinesia (PCD) is a clinically and genetically heterogeneous ciliopathy. Dysfunction of motile respiratory and nodal cilia results in sinopulmonary symptoms associated with laterality defects (LD) found in half of the patients. The molecular basis of the disease is insufficiently investigated in patients originating from the Arabian Peninsula. In a group of 16 unrelated Saudi patients clinically suspected of PCD and among whom only 5 (31%) had LD, we first screened by PCR-RFLP two founder mutations, RSPH9 c.804_806del and CCDC39 c.2190del previously identified in patients from the Arabian Peninsula and Tunisia, respectively. When negative, targeted panel or whole-exome sequencing was performed. Three patients were homozygous for the mutation in RSPH9, which encodes an axonemal protein that is absent from nodal cilia. None of the patients carried the CCDC39 founder mutation frequent in Tunisia. NGS analysis showed that nine patients had homozygous mutations in PCD genes. In total, sequential RFLP and NGS analysis solved 75% (12/16) of cases and identified ten distinct mutations, among which six are novel, in nine different genes. These results, which highlight the genetic heterogeneity of PCD in Saudi Arabia, show that the RSPH9 c.804_806del mutation is a prevalent mutation among Saudi patients, whereas the CCDC39 c.2190del ancestral allele is most likely related to the Berber population. This study shows that RSPH9 founder mutation first-line screening and NGS analysis is efficient for the genetic exploration of PCD in Saudi patients. The RSPH9 founder mutation accounts for the low rate of LD among Saudi patients.

Pathogenic variants identified using whole-exome sequencing in Chinese patients with primary ciliary dyskinesia.

The genetic factors contributing to primary ciliary dyskinesia (PCD), a rare autosomal recessive disorder, remain elusive for ~20%-35% of patients with complex and abnormal clinical phenotypes. Our study aimed to identify causative variants of PCD-associated pathogenic candidate genes using whole-exome sequencing (WES). All patients were diagnosed with PCD based on clinical phenotype or transmission electron microscopy images of cilia. WES and bioinformatic analysis were then conducted on patients with PCD. Identified candidate variants were validated by Sanger sequencing. Pathogenicity of candidate variants was then evaluated using in silico software and the American College of Medical Genetics and Genomics (ACMG) database. In total, 13 rare variants were identified in patients with PCD, among which were three homozygous causative variants (including one splicing variant) in the PCD-associated genes CCDC40 and DNAI1. Moreover, two stop-gain heterozygous variants of DNAAF3 and DNAH1 were classified as pathogenic variants based on the ACMG criteria. This study identified novel potential pathogenic genetic factors associated with PCD. Noteworthy, the patients with PCD carried multiple rare causative gene variants, thereby suggesting that known causative genes along with other functional genes should be considered for such heterogeneous genetic disorders.

Inhaled delivery of a lipid nanoparticle encapsulated messenger RNA encoding a ciliary protein for the treatment of primary ciliary dyskinesia.

Primary ciliary dyskinesia (PCD) is a respiratory disease caused by dysfunction of the cilia with currently no approved treatments. This predominantly autosomal recessive disease is caused by mutations in any one of over 50 genes involved in cilia function; DNAI1 is one of the more frequently mutated genes, accounting for approximately 5-10% of diagnosed PCD cases. A codon-optimized mRNA encoding DNAI1 and encapsulated in a lipid nanoparticle (LNP) was administered to mice via aerosolized inhalation resulting in the expression human DNAI1 in the multiciliated cells of the pseudostratified columnar epithelia. The spatial localization of DNAI1 expression in the bronchioles indicate that delivery of the DNAI1 mRNA transpires the lower airways. In a PCD disease model, exposure to the LNP-encapsulated DNAI1 mRNA resulted in increased ciliary beat frequency using high speed videomicroscopy showing the potential for an mRNA therapeutic to correct cilia function in patients with PCD due to DNAI1 mutations.

Clinical and genetic features of primary ciliary dyskinesia in a cohort of consecutive clinically suspect children in western China.

BACKGROUND: Primary ciliary dyskinesia (PCD) is a rare, inherited disorder of the motile cilia that exhibits genetic and clinical heterogeneity among different populations. PCD diagnosis remains challenging owing to the heterogeneity of associated clinical features and lack of a gold standard diagnostic test. OBJECTIVE: The aim of this study was to analyze the clinical and genetic characteristics of a group of children with clinically suspected PCD in one region of China, with the goal of providing a more robust knowledge base regarding the genetic stratification underlying this disease in Chinese populations. METHODS: We retrospectively analyzed the data from 38 patients with clinically suspected PCD who had undergone next-generation sequencing (NGS) between November 2016 and March 2021 in the respiratory department of a tertiary Children's hospital in Western China. The genetic features of the confirmed cases were summarized by reviewing data associated with other cohorts of Chinese children. RESULTS: Overall, 16 patients were ultimately diagnosed with PCD with a median age of 8.5 years. All patients presented with a chronic wet cough, 93.75% exhibited chronic or recurrent sinusitis/rhinitis, 43.75% experienced recurrent wheezing, 56.25% reported respiratory symptoms present since infancy, 31.25% had a history of neonatal respiratory distress (NRD), and 25% exhibited otitis media. Only 18.75% of these patients exhibited laterality defects. High frequencies of DNAH11 mutations were detected by integrating data from PCD patient cohorts in China. CONCLUSION: The high frequency of DNAH11 mutations may limit the utility of transmission electron microscopy (TEM) as a first-line approach to diagnosing PCD in China in the absence of other indicators.

Progress in diagnosis of primary ciliary dyskinesia.

Primary ciliary dyskinesia (PCD) is an autosomal recessive genetic disorder characterised by motor ciliary dysfunction. The main manifestations are bronchiectasis, chronic sinusitis and situs inversus (viscera translocation triad). Additionally, it can present as male infertility and female ectopic pregnancy. However, there is currently no recognised diagnostic standard for PCD, which brings great challenges to its diagnosis and treatment. In addition to clinical data, the current diagnostic methods of PCD mainly include PICADAR, nasal exhaled nitric oxide, transmission electron microscopy, high-resolution immunofluorescence, high-speed video microscopy analysis and gene detection. This article makes a comprehensive comparison of the above diagnostic methods and suggests that genetic detection technology will become the general trend of PCD diagnosis.

Fissure adjacent partial lobe atelectasis in primary ciliary dyskinesia.

AIM: Establishing the underlying cause in a child with chronic suppurative lung disease (CSLD) allows for targeted treatment and screening for associated complications. One cause of CSLD is primary ciliary dyskinesia (PCD). Testing for PCD requires specialist expertise which is not widely available. Computed tomography (CT) scans are commonly performed when assessing CSLD. Identifying PCD-specific signs on CT would help clinicians in deciding when to refer for specialist testing. One potential PCD-specific sign we have observed is fissure adjacent partial lobe atelectasis (FAPLA). We aimed to assess if FAPLA is commonly found in CT of PCD patients. METHODS: Fifty-eight CT scans from 42 adult and child PCD patients were analysed. The presence and distribution of FAPLA were noted, and its association to sputum culture and other signs commonly seen in CSLD (bronchiectasis, bronchial wall thickening, air trapping and mucus plugging). RESULTS: FAPLA was found in 13 of 40 participants in their earliest CT scan. The prevalence of FAPLA was similar in children and adults. FAPLA involved the right middle lobe in all 13 cases and was systematically associated with ≥1 other structural change. There was no association between FAPLA and bacterial isolation from sputum. CONCLUSION: FAPLA was found in 32.5% PCD scans, without difference between children and adults in terms of frequency. Future work will determine if it is a PCD-specific sign by assessing whether it is also found in other CSLD processes and analysing more scans from children with PCD to determine how early this sign develops.

[Pathogenic genes and corresponding ciliary defects associated with primary ciliary dyskinesia].

Primary ciliary dyskinesia (PCD) is a recessive genetic disorder of motile cilia with substantial genetic and phenotypic heterogeneity. Clinical features of PCD vary from one patient to another, and no single test has the sensitivity and specificity to accurately diagnose PCD. Genetic testing combined with other auxiliary tests can facilitate the confirmatory diagnosis of PCD. So far more than 40 genes have been associated with PCD, but most research have focused on common genes, which hinders our understanding of other rare PCD-genes. This review has summarized the PCD-associated genes and the corresponding characteristics of dysfunctional cilia, with an aim to provide a basis for early identification of such diseases.

[Sinusitis, otitis media and diffuse bronchiectasis in both lungs].

Primary ciliary dyskinesia (PCD) is a rare autosomal recessive or X-linked biallelic mutations inherited disease, characterized by motile cilia dysfunction. Typical manifestations include bronchiectasis, secretory otitis media, sinusitis, situs inversus, and infertility. PCD often needs to be differentiated from cystic fibrosis (CF) because of similar clinical manifestations. In this paper, a juvenile female who presented with recurrent cough and expectoration with fever since early childhood, had a history of secretory otitis media and sinusitis, and had been considered for the diagnosis of CF. After the discovery of compound heterozygous mutations in PCD related pathogenic genes by gene sequencing, combined with the clinical manifestations and imaging characteristics, PCD was finally diagnosed.

Clinical phenotypes of primary ciliary dyskinesia. / 原发性纤毛运动障碍的临床表型.

Primary ciliary dyskinesia (PCD) is a hereditary disease characterized by airway mucociliary clearance dysfunction. The estimated prevalence of PCD is 1꞉10 000 to 1꞉20 000. The main respiratory manifestations in children are cough, expectoration, chronic rhinitis, sinusitis, and chronic otitis media, while the most common symptoms in adults are chronic sinusitis, bronchiectasis, and infertility. About 50% of patients with certain PCD-related gene variants are combined with situs inversus, and the incidence of congenital heart disease is also high. The pathogenesis behind PCD is that gene variants cause structural or functional disorders of respiratory cilia and motile cilia of other organs, leading to a series of heterogeneous clinical manifestations, which makes it difficult to identify and diagnose PCD. Combining different disease screening tools and understanding the relationship between genotypes and phenotypes may facilitate early diagnosis and treatment for PCD.

Topological data analysis reveals genotype-phenotype relationships in primary ciliary dyskinesia.

BACKGROUND: Primary ciliary dyskinesia (PCD) is a heterogeneous inherited disorder caused by mutations in approximately 50 cilia-related genes. PCD genotype-phenotype relationships have mostly arisen from small case series because existing statistical approaches to investigating relationships have been unsuitable for rare diseases. METHODS: We applied a topological data analysis (TDA) approach to investigate genotype-phenotype relationships in PCD. Data from separate training and validation cohorts included 396 genetically defined individuals carrying pathogenic variants in PCD genes. To develop the TDA models, 12 clinical and diagnostic variables were included. TDA-driven hypotheses were subsequently tested using traditional statistics. RESULTS: Disease severity at diagnosis, measured by forced expiratory volume in 1 s (FEV1) z-score, was significantly worse in individuals with CCDC39 mutations (compared to other gene mutations) and better in those with DNAH11 mutations; the latter also reported less neonatal respiratory distress. Patients without neonatal respiratory distress had better preserved FEV1 at diagnosis. Individuals with DNAH5 mutations were phenotypically diverse. Cilia ultrastructure and beat pattern defects correlated closely to specific causative gene groups, confirming these tests can be used to support a genetic diagnosis. CONCLUSIONS: This large scale, multi-national study presents PCD as a syndrome with overlapping symptoms and variations in phenotype according to genotype. TDA modelling confirmed genotype-phenotype relationships reported by smaller studies (e.g. FEV1 worse with CCDC39 mutation) and identified new relationships, including FEV1 preservation with DNAH11 mutations and diversity of severity with DNAH5 mutations.

Higher throughput drug screening for rare respiratory diseases: readthrough therapy in primary ciliary dyskinesia.

BACKGROUND: Development of therapeutic approaches for rare respiratory diseases is hampered by the lack of systems that allow medium-to-high-throughput screening of fully differentiated respiratory epithelium from affected patients. This is a particular problem for primary ciliary dyskinesia (PCD), a rare genetic disease caused by mutations in genes that adversely affect ciliary movement and consequently mucociliary transport. Primary cell culture of basal epithelial cells from nasal brush biopsies followed by ciliated differentiation at the air-liquid interface (ALI) has proven to be a useful tool in PCD diagnostics but the technique's broader utility, including in pre-clinical PCD research, has been restricted by the limited number of basal cells that can be expanded from such biopsies. METHODS: We describe an immunofluorescence screening method, enabled by extensive expansion of basal cells from PCD patients and the directed differentiation of these cells into ciliated epithelium in miniaturised 96-well transwell format ALI cultures. As proof-of-principle, we performed a personalised investigation in a patient with a rare and severe form of PCD (reduced generation of motile cilia), in this case caused by a homozygous nonsense mutation in the MCIDAS gene. RESULTS: Initial analyses of ciliary ultrastructure, beat pattern and beat frequency in the 96-well transwell format ALI cultures indicate that a range of different PCD defects can be retained in these cultures. The screening system in our proof-of-principal investigation allowed drugs that induce translational readthrough to be evaluated alone or in combination with nonsense-mediated decay inhibitors. We observed restoration of basal body formation but not the generation of cilia in the patient's nasal epithelial cells in vitro. CONCLUSION: Our study provides a platform for higher throughput analyses of airway epithelia that is applicable in a range of settings and suggests novel avenues for drug evaluation and development in PCD caused by nonsense mutations.

Primary Ciliary Dyskinesia.

Primary ciliary dyskinesia (PCD) is an inherited cause of bronchiectasis. The estimated PCD prevalence in children with bronchiectasis is up to 26% and in adults with bronchiectasis is 1 to 13%. Due to dysfunction of the multiple motile cilia of the respiratory tract patients suffer from poor mucociliary clearance. Clinical manifestations are heterogeneous; however, a typical patient presents with chronic productive cough and rhinosinusitis from early life. Other symptoms reflect the multiple roles of motile cilia in other organs and can include otitis media and hearing loss, infertility, situs inversus, complex congenital heart disease, and more rarely other syndromic features such as hydrocephalus and retinitis pigmentosa. Awareness, identification, and diagnosis of a patient with PCD are important for multidisciplinary care and genetic counseling. Diagnosis can be pursued through a multitest pathway which includes the measurement of nasal nitric oxide, sampling the nasal epithelium to assess ciliary function and structure, and genotyping. Diagnosis is confirmed by the identification of a hallmark ultrastructural defect or pathogenic mutations in one of > 45 PCD causing genes. When a diagnosis is established management is centered around improving mucociliary clearance through physiotherapy and treatment of infection with antibiotics. The first international randomized controlled trial in PCD has recently been conducted showing azithromycin is effective in reducing exacerbations. It is likely that evidence-based PCD-specific management guidelines and therapies will be developed in the near future. This article examines prevalence, clinical features, diagnosis, and management of PCD highlighting recent advances in basic science and clinical care.

The Primary Ciliary Dyskinesia Computed Tomography Score in Adults with Bronchiectasis: A Derivation und Validation Study.

BACKGROUND: Primary ciliary dyskinesia (PCD) is a rare genetic disorder which requires a complex diagnostic workup. Thus, an easy and widely available screening method would be helpful to identify patients who need a further diagnostic workup for PCD. OBJECTIVES: The aim of the study was to develop and validate a computed tomography (CT) score for PCD to facilitate etiological diagnosis in adults with bronchiectasis. METHOD: Chest CTs from 121 adults with bronchiectasis were scored for bronchiectasis morphology, distribution, and associated findings. Patients with and without the etiological diagnosis of PCD (46 and 75, respectively) were compared. Significantly, different imaging findings (p < 0.05) in univariate analysis were considered for multivariate analysis. Distinct findings were used to build the score. Based on this score, receiver operating characteristic (ROC) curve analysis was performed. The score was validated with 2 independent cohorts, another cohort from the same institution with 56 patients (28 with PCD) and an external cohort from another referral center with 172 patients (86 with PCD). RESULTS: The following parameters predicted PCD in adults with bronchiectasis and were included in the score with weighting according to their regression coefficients: 2 points were given for predominance in the middle/lower lobe, 2 points for tree-in-bud pattern, 2 points for atelectasis or prior resection of a middle/lower lobe, and 3 points for absence of emphysema and fibrosis. Situs inversus was only observed in subjects with PCD (Kartagener syndrome) and, thus, was not used in the primary ciliary dyskinesia computed tomography (PCD-CT) score as group comparisons could not be performed. ROC curve analysis revealed an area under the curve (AUC) of 0.90 (95% CI 0.85-0.96). Youden index was the highest at a threshold of >6 with a sensitivity of 83% and a specificity of 83%. In the validation cohorts, ROC curve analysis confirmed the performance of the score with an AUC of 0.83 (95% CI 0.72-0.94) in the first validation cohort and 0.79 (95% CI 0.73-0.86) in the external validation cohort. CONCLUSIONS: The PCD-CT score provides the first validated CT score for PCD and helps physicians in identifying adult bronchiectasis patients who require further diagnostic workup. Key message: The PCD-CT score provides the first validated CT score to assist physicians in identifying adult bronchiectasis patients who require a further diagnostic workup for PCD. It potentially improves earlier recognition of this rare and underdiagnosed disease.