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Background: Primary Ciliary Dyskinesia (PCD) is a rare genetic disorder requiring airway clearance techniques for mucus removal. We aimed to evaluate the feasibility and the effect of the active cycle of breathing technique (ACBT) versus oscillating positive expiratory pressure therapy (OPEP) in improving lung function and functional exercise capacity among children with PCD in Palestine. Methods: 32 PCD children (6–18 years) were included in a 12-week home-based feasibility study. They were assigned randomly into two groups: ACBT and OPEP. Data collection included spirometry measurements, and the six-minute walk test (6MWT). Results: After 12 weeks of regular airway clearance techniques (ACT), the FEV1, MEF25-75%, and the 6MWT demonstrated statistically significant differences (p = .02, p = .04, and p = .05 respectively) between the two groups, in favor of the OPEP group with the effect size of Cohen’s d (0.86, 0.76, and 0.71) respectively. However, there was no significant difference (p > .05) between the two groups in FVC and FEV1/FVC. Additionally, only in the OPEP group, significant differences were recorded between pre and post-tests for FEV1 and 6MWT (p < .05). Conclusion: The randomized study design comparing ACBT and OPEP was feasible and acceptable to patients. OPEP demonstrates potential for managing respiratory health; however, treatments should be individualized to address each patient’s specific needs. Further research with larger cohorts is needed to assess the effectiveness of both methods.

Background Primary ciliary dyskinesia (PCD) is a rare genetical disease with malfunction of the motile cilia leading to impaired muco-ciliary clearance in the respiratory tract. There is no cure for PCD, only supportive therapy aimed at minimizing the progression of the disease and improving the patient’s quality of life (QoL). Physical activity (PA) is one of these recommended supportive therapies for people with PCD (pwPCD). However, there is no scientific evidence to support this recommendation. In addition, regular medical advice to increase PA remains largely ineffective in pwPCD. Methods To test the main hypothesis, that an individualized and supported PA program leads to a better QoL 6 months after randomization (QoL-PCD questionnaire) compared to usual recommendation in pwPCD, 158 pwPCD aged 7 to 55 years are to be included in this multi-center randomized controlled trial (RCT). After the screening visit, a 1:1 randomization stratified by age group and FEV1 will be performed. A QoL-PCD questionnaire, motor test, and lung function will be carried out at regular intervals in both groups. PA is recorded in both groups using activity trackers during the study period. The main aim of the trial is to estimate the difference in the change of QoL between the groups after 6 months. Therefore, our full analysis set consists of all randomized patients and analysis is performed using the intention-to-treat principle. Statistical software R ( http://www.r-project.org ) is used. Ethical approvement without any reservations: RUB Bochum Ethics Committee (No. 23–7938; December 4, 2023). Recruitment start: March 2024. Discussion Limitations result from the rarity of PCD with its broad disease spectrum and the large age range. These are reduced by stratified randomization and the measurement of the individual change in QoL as primary endpoint. In our view, only a PA program tailored to individual needs with close contact to trainers offers the chance to meet personal needs of pwPCD and to establish PA as a pillar of therapy in the long term. The study protocol explains all procedures and methods of recruitment, implementation of the study visits and intervention, measures for patient and data safety, and for minimizing risks and bias. Trial registration German Clinical Trials Register (DRKS) 00033030. Registered on December 7, 2023. Update 10 July 2024. Study protocol version 10 Version 1.2; 12 June 2024

Introduction Kartagener syndrome is a subset of a larger group of ciliary motility disorders called primary ciliary dyskinesias. The syndrome includes the clinical triad of chronic sinusitis, bronchiectasis, and situs inversus. Patients usually present with recurrent respiratory tract infections due to ineffective mucociliary clearance. Females and males are equally affected. Kartagener syndrome occurs in about 1 in 32,000 to 40,000 births worldwide. Case presentation This case involved a 17-year-old Black African Semitic male patient who presented to our hospital with a complaint of intermittent productive cough, which started when he was 5 years old. He had a history of repeated treatment for lower respiratory tract infection and chronic sinusitis with frequent exacerbation. On examination, he had coarse crackles over the left posterior lower lung field. Heart sounds were appreciated on the right side. During imaging investigations, his chest X-ray posterior-anterior view showed dextrocardia and right side gastric shadow with left paracardiac bronchiectatic changes. A high-resolution chest computed tomography scan was suggestive of complete situs inversus. There were left lower lobe bronchiectatic changes. An electrocardiogram showed features of dextrocardia. Routine laboratory tests were within normal range. He was treated with thoracic physiotherapy, azithromycin 500 mg three times per week, and mucolytics, with no apparent exacerbations in the last 6 months. Conclusion The diagnosis of Kartagener syndrome is typically delayed because the clinical symptoms are easily mistaken for common infections. Since there is no specific treatment for Kartagener syndrome, early diagnosis and management of Kartagener syndrome are critical to prevent irreversible lung damage and chronic lifelong sequelae. A high index of suspicion is needed to make an early diagnosis so that timely treatment options may be offered to prevent problems associated with Kartagener syndrome.

Primary ciliary dyskinesia (PCD) is a genetically heterogeneous recessive disorder of motile cilia that leads to oto-sino-pulmonary diseases and organ laterality defects in approximately 50% of cases. The estimated incidence of PCD is approximately 1 per 15,000 births, but the prevalence of PCD is difficult to determine, primarily because of limitations in diagnostic methods that focus on testing ciliary ultrastructure and function. Diagnostic capabilities have recently benefitted from (1) documentation of low nasal nitric oxide production in PCD and (2) discovery of biallelic mutations in multiple PCD-causing genes. The use of these complementary diagnostic approaches shows that at least 30% of patients with PCD have normal ciliary ultrastructure. More accurate identification of patients with PCD has also allowed definition of a strong clinical phenotype, which includes neonatal respiratory distress in >80% of cases, daily nasal congestion and wet cough starting soon after birth, and early development of recurrent/chronic middle-ear and sinus disease. Recent studies, using advanced imaging and pulmonary physiologic assessments, clearly demonstrate early onset of lung disease in PCD, with abnormal air flow mechanics by age 6-8 years that is similar to cystic fibrosis, and age-dependent onset of bronchiectasis. The treatment of PCD is not standardized, and there are no validated PCD-specific therapies. Most patients with PCD receive suboptimal management, which should include airway clearance, regular surveillance of pulmonary function and respiratory microbiology, and use of antibiotics targeted to pathogens. The PCD Foundation is developing a network of clinical centers, which should improve diagnosis and management of PCD.

Background Clinical management of primary ciliary dyskinesia (PCD) respiratory disease is currently based on improving mucociliary clearance and controlling respiratory infections, through the administration of antibiotics. Treatment practices in PCD are largely extrapolated from more common chronic respiratory disorders, particularly cystic fibrosis, but no randomized controlled trials (RCT) have ever evaluated efficacy and safety of any pharmacotherapeutics used in the treatment of PCD. Maintenance therapy, with the macrolide antibiotic azithromycin, is currently widely used in chronic respiratory diseases including PCD. In addition to its antibacterial properties, azithromycin is considered to have beneficial anti-inflammatory and anti-quorum-sensing properties. The aim of this study is to determine the efficacy of azithromycin maintenance therapy for 6 months on respiratory exacerbations in PCD. The secondary objectives are to evaluate the efficacy of azithromycin on lung function, ventilation inhomogeneity, hearing impairment, and symptoms (respiratory, sinus, ears and hearing) measured on a PCD-specific health-related quality of life instrument, and to assess the safety of azithromycin maintenance therapy in PCD. Methods The BESTCILIA trial is a European multi-centre, double-blind, randomized, placebo-controlled, parallel group study. The intervention is tablets of azithromycin 250/500 mg according to body weight or placebo administered three times a week for 6 months. Subjects with a confirmed diagnosis of PCD, age 7–50 years, are eligible for inclusion. Chronic pulmonary infections with Gram-negative bacteria or any recent occurrence of non-tuberculous mycobacteria are exclusion criteria. The planned number of subjects to be included is 125. The trial has been approved by the Research Ethics Committees of the participating institutions. Discussion We present a study protocol of an ongoing RCT, evaluating for the first time, the efficacy and safety of a pharmacotherapeutic treatment for patients with PCD. The RCT evaluates azithromycin maintenance therapy, a drug already commonly prescribed in other chronic respiratory disorders. Furthermore, the trial will utilize the Lung clearance index and new, PCD-specific quality of life instruments as outcome measures for PCD. Recruitment is hampered by frequent occurrence of Pseudomonas aeruginosa infection, exacerbations at enrolment, and the patients’ perception of disease severity and necessity of additional management and treatment during trial participation. Trial registration EudraCT 2013-004664-58 (date of registration: 2014-04-08).

BackgroundPrimary ciliary dyskinesia (PCD) is a rare autosomal recessive genetic disorder characterised by dysfunction of motile cilia. Ciliary dysmotility causes poor mucociliary clearance and leads to impairment of pulmonary function and severe respiratory infections. PCD has no specific therapy. With the aim to permanently restore gene function and normalise ciliary motility, we used gene editing to replace mutated with wild-type sequence in defective cells.MethodsThe target gene was dynein heavy chain 11 (DNAH11), an essential component of ciliary structure. Airway ciliated cells were collected from two patients with PCD with DNAH11 nonsense mutations and altered ciliary beating and pattern. Repair of the genetic defect was performed ex vivo by site-specific recombination using transcription activator-like effector nucleases (TALENs).ResultsIn an epithelial cell line engineered to contain the DNAH11 target site, TALENs cleaved over 80% of the mutated DNAH11 sequence and replaced the mutated sequence with wild-type sequence in about 50% of cells. In airway ciliated cells of patients with PCD, site-specific recombination and normalisation of ciliary beating and pattern occurred in 33% and 29% of cells, respectively.ConclusionThis study demonstrates that gene editing can rescue ciliary beating ex vivo, opening up new avenues for treating PCD.

Primary ciliary dyskinesia (PCD) is usually inherited as an autosomal recessive disorder and presents with upper and lower respiratory tract infection, and mirror image arrangement in around 50% of cases. Cilia dysfunction is also implicated in a wider spectrum of disease, including polycystic liver and kidney disease, central nervous system problems including retinopathy and hydrocephalus, and biliary atresia. Cilia are complex structures, containing more than 250 proteins; recent studies have begun to locate PCD genes scattered throughout the genome. Screening tests for PCD include nasal nitric oxide and in vivo tests of ciliary motility such as the saccharin test. Specific diagnosis requires examination of cilia by light and electron microscopy, with epithelial culture in doubtful cases. This is only available in supra-regional centres, recently centrally funded by the National Commissioning Group. Treatment is not evidence based and recommendations are largely extrapolated from cystic fibrosis and other suppurative lung diseases.

•Recent improvements in genetic testing have shown a greatly increased prevalence of PCD, suggesting a significant cohort of undiagnosed patients.•PCD should be considered in individuals with a history neonatal respiratory distress, a chronic productive cough, chronic rhinosinusitis and organ laterality defects.•Diagnosis of PCD is contingent on identifying specific clinical symptoms and investigations such as nasal nitric oxide, ciliary microscopy and genetic testing.•Clinical management should focus on airway clearance and robust treatment of acute infections. Primary ciliary dyskinesia (PCD) is a rare genetic disorder characterised by abnormal function of motile cilia. The condition usually manifests in early life with neonatal distress, chronic sinopulmonary disease and organ laterality disorders. In adults, it is an underdiagnosed cause of bronchiectasis as well as subfertility. This review provides an overview of PCD for clinicians. We discuss its aetiology, its presentation, how it is diagnosed and its multidisciplinary clinical management.

Primary ciliary dyskinesia (PCD) is a rare genetic disorder with a variable clinical phenotype that is accompanied by reduced motility of the cilia in the respiratory tract and numerous other organs. This leads to various characteristic symptoms and disease manifestations, primarily affecting the lungs (chronic persistent productive cough, bronchiectasis), the nose and paranasal sinuses (chronic persistent rhinitis or rhinosinusitis) as well as the middle ear (chronic otitis media, middle ear effusion). Moreover, PCD is associated with impaired fertility or lateralization defects (situs anomalies, congenital heart defects). The diagnostics of PCD are complex and require a combination of several sophisticated instrument-based diagnostic procedures. Through thorough history taking and evaluation, suspected cases can be comparatively well identified based on typical clinical features and referred to further diagnostics. In recent years, molecular genetic analysis through panel diagnostics or whole exome and whole genome sequencing, has gained in importance as this enables affected individuals to participate in disease-specific and genotype-specific clinical trials. Although the current treatment is purely symptomatic, the earliest possible diagnosis is crucial for connecting patients to specialized PCD centers, which can have a significant impact on the clinical course of the affected individuals.

Kartagener's syndrome (KS) is an autosomal recessive genetic disease accounting for approximately 50% of the cases of primary ciliary dyskinesia (PCD). As it is accompanied by many complications, PCD/KS severely affects the patient's quality of life. Therapeutic approaches for PCD/KS aim to enhance prevention, facilitate rapid definitive diagnosis, avoid misdiagnosis, maintain active treatment, control infection and postpone the development of lesions. In male patients, sperm flagella may show impairment in or complete absence of the ability to swing, which ultimately results in male infertility. Assisted reproductive technology will certainly benefit such patients. For PCD/KS patients with completely immotile sperm, intracytoplasmic sperm injection may be very important and even indispensable. Considering the number of PCD/KS susceptibility genes and mutations that are being identified, more extensive genetic screening is indispensable in patients with these diseases. Moreover, further studies into the potential molecular mechanisms of these diseases are required. In this review, we summarize the available information on various aspects of this disease in order to delineate the therapeutic objectives more clearly, and clarify the efficacy of assisted reproductive technology as a means of treatment for patients with PCD/KS-associated infertility.