ABSTRACT
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.
Subject(s)
Multicenter Studies as Topic , Quality of Life , Humans , Adolescent , Child , Young Adult , Adult , Middle Aged , Male , Female , Exercise , Longitudinal Studies , Exercise Therapy/methods , Equivalence Trials as Topic , Treatment Outcome , Time Factors , Randomized Controlled Trials as Topic , Surveys and Questionnaires , Ciliary Motility Disorders/therapy , Kartagener Syndrome/therapy , Kartagener Syndrome/physiopathologyABSTRACT
Primary ciliary dyskinesia (PCD) is a rare, genetic disease characterized by dysfunctional motile cilia and abnormal mucociliary clearance, resulting in chronic sino-oto-pulmonary disease, neonatal respiratory distress, subfertility, and organ laterality defects. Over the past 2 decades, research and international collaborations have led to an improved understanding of disease prevalence, classic and variable phenotypes, novel diagnostics, genotype-phenotype correlations, long term morbidity, and innovative therapeutics. However, PCD is often underrecognized in clinical settings and the recent analyses of genetic databases suggest that only a fraction of these patients are being accurately diagnosed. Knowledge of significant advancements, from pathophysiology to the expanded range of clinical manifestations, will have important clinical impacts. These may include increasing disease recognition, improving diagnostic testing and management, and establishing an adequate pool of affected patients to enroll in upcoming clinical therapeutic trials. The objective of this state-of-the-art review is for readers to gain a greater understanding of the clinical spectrum of motile ciliopathies, cutting-edge diagnostic practices, emerging genotype-phenotype associations, and currently accepted management of people with PCD.
Subject(s)
Kartagener Syndrome , Humans , Kartagener Syndrome/diagnosis , Kartagener Syndrome/therapy , Kartagener Syndrome/genetics , Phenotype , Ciliary Motility Disorders/diagnosis , Ciliary Motility Disorders/genetics , Ciliary Motility Disorders/therapyABSTRACT
This work aimed to conduct a comparative study between cystic fibrosis and primary ciliary dyskinesia among adolescents and their caregivers to understand their emotional adaptation to the disease. Thirty-nine dyads of adolescents aged 9-18 years and their primary caregivers were assessed, 69.20 % of whom had a diagnosis of cystic fibrosis. For the adolescents, anxious-depressive symptomatology was assessed using the HADS, perceived threat of disease (B-IPQ) and quality of life (CRQ-SAS). For the caregivers, emotional symptomatology (HADS) and perceived stress levels (PIP) were assessed. Mean comparisons were made according to diagnosis and severity of anxious-depressive symptomatology, relationships between variables were studied, and qualitative comparative analysis models, QCA, were performed. Higher levels of anxiety and depression were found in the caregiver than in the adolescent. Adolescents with primary ciliary dyskinesia have a more significant emotional impact than adolescents with cystic fibrosis. However, no differences were found in caregivers according to diagnosis. The adolescent's emotional state, quality of life and perceived threat of disease were related to and explained by the caregiver's emotional state, and vice versa. Therefore, there appears to be a certain degree of emotional contagion between the dyad members. This is a preliminary study that has not been carried out before and can help to understand the psychological aspects associated with these diseases to favour the patient's adjustment and thereby ensure more effective management of the disease and adherence to treatment. (AU)
El objetivo fue realizar un estudio comparativo entre la fibrosis quística y la discinesia ciliar primaria entre adolescentes y sus cuidadores para comprender su adaptación a la enfermedad. Evaluando 39 díadas de adolescentes de entre 9 y 18 años y sus cuidadores, el 69,20% de los cuales tenían un diagnóstico de fibrosis quística. Para los adolescentes, se evaluó la sintomatología ansioso-depresiva mediante el HADS, la amenaza percibida de la enfermedad (B-IPQ) y la calidad de vida (CRQ-SAS). Para los cuidadores, se evaluó la sintomatología emocional (HADS) y los niveles de estrés percibido (PIP). Se realizaron comparaciones de medias según el diagnóstico y la sintomatología ansioso-depresiva, se estudiaron las relaciones entre variables y se realizaron modelos de análisis cualitativo comparativo. Se encontraron mayores niveles ansioso-depresivos en el cuidador que en el adolescente. Los adolescentes con discinesia ciliar primaria presentan un impacto emocional mayor que los adolescentes con fibrosis quística. No se encontraron diferencias en los cuidadores según el diagnóstico. El estado emocional, la calidad de vida y la percepción de amenaza de la enfermedad del adolescente estaban relacionados con el estado emocional del cuidador y se explicaban por él, y viceversa. Por lo tanto, parece existir cierto grado de contagio emocional entre los miembros de la díada. Se trata de un estudio preliminar que no se ha realizado previamente y que ayuda a comprender los aspectos psicológicos asociados a estas enfermedades favoreciendo el ajuste del paciente y asegurar así un manejo más eficaz de la enfermedad y la adherencia al tratamiento. (AU)
Subject(s)
Humans , Male , Female , Adolescent , Adult , Cystic Fibrosis/psychology , Cystic Fibrosis/therapy , Ciliary Motility Disorders/psychology , Ciliary Motility Disorders/therapy , Caregivers/psychologyABSTRACT
Primary ciliary dyskinesia (PCD) is a genetic disease characterized by defects in motile cilia, which play an important role in several organ systems. Lung disease is a hallmark of PCD, given the essential role of cilia in airway surface defense. Diagnosis of PCD is complicated due to its reliance on complex tests that are not utilized by every clinic and also its phenotypic overlap with several other respiratory diseases. Nonetheless, PCD is increasingly being recognized as more common than once thought. The disease is genetically complex, with several genes reported to be associated with PCD. There is no cure for PCD, but gene therapy remains a promising therapeutic strategy. In this review, we provide an overview of the clinical symptoms, diagnosis, genetics, and current treatment regimens for PCD. We also describe PCD model systems and discuss the therapeutic potential of different gene therapeutics for targeting the intended cellular target, the ciliated cells of the airway.
Subject(s)
Cilia , Ciliary Motility Disorders , Humans , Cilia/genetics , Genetic Therapy , Models, Biological , Ciliary Motility Disorders/genetics , Ciliary Motility Disorders/therapyABSTRACT
INTRODUCTION: There are no recent data on primary ciliary dyskinesia (PCD) distribution, diagnosis and treatment in Italy. METHODS: A descriptive study based on a survey questionnaire. It consisted of three sections (patients, diagnosis, and treatment), and sent to all the Italian PCD Centers. RESULTS: Questionnaires obtained from 20/22 centers in 12/20 regions showed that the total number of PCD patients treated at the participating centers was of 416. Out of all centers, 55% follow <20 patients, two centers have >40 patients, and 75% follow both pediatric and adults. Age at diagnosis was between 4 and 8 years in 45% of the centers, <3 years in three centers. Nasal nitric oxide, transmission electron microscopy and ciliary high-speed video microscopy are performed in 75%, 90%, and 40% of centers, respectively. Immunofluorescence is available in five centers. Genetic analysis is offered in 55% of the centers, and in seven centers >50% of the patients have a known genetic profile. Patients treated at all centers receive inhaled saline solutions, corticosteroids and chest physiotherapy. Prophylactic antibiotics and mucolytics are prescribed in 95% and 50% of the centers, respectively. Pseudomonas infection is treated with oral or inhaled antibiotics. CONCLUSIONS: Many Italian centers care for a small number of pediatric and adult patients, and diagnosis is often delayed. We found a great variability in the available diagnostic procedures, as well in the prescribed therapies. Our study will help to uniform diagnostic algorithm and share treatments protocols for PCD in Italy and allowed to set specific national goals.
Subject(s)
Ciliary Motility Disorders , Kartagener Syndrome , Adult , Humans , Child , Child, Preschool , Kartagener Syndrome/diagnosis , Kartagener Syndrome/therapy , Kartagener Syndrome/genetics , Microscopy, Electron, Transmission , Anti-Bacterial Agents/therapeutic use , Italy , Surveys and Questionnaires , Ciliary Motility Disorders/diagnosis , Ciliary Motility Disorders/therapy , CiliaABSTRACT
Primary ciliary dyskinesia (PCD) can be defined as a multiorgan ciliopathy with a dominant element of chronic airway disease affecting the nose, sinuses, middle ear, and in particular, the lower airways. Although most patients with PCD are diagnosed during preschool years, it is obvious that the chronic lung disease starts its course already from birth. The many faces of the clinical picture change, as does lung function, structural lung damage, the burden of infection, and of treatment throughout life. A markedly severe neutrophil inflammation in the respiratory tract seems pervasive and is only to a minimal extent ameliorated by a treatment strategy, which is predominantly aimed at bacterial infections. An ever-increasing understanding of the different aspects, their interrelationships, and possible different age courses conditioned by the underlying genotype is the focus of much attention. The future is likely to offer personalized medicine in the form of mRNA therapy, but to that end, it is of utmost importance that all patients with PCD be carefully characterized and given a genetic diagnosis. In this narrative review, we have concentrated on lower airways and summarized the current understanding of the chronic airway disease in this motile ciliopathy. In addition, we highlight the challenges, gaps, and opportunities in PCD lung disease research.
Subject(s)
Ciliary Motility Disorders , Ciliopathies , Pulmonary Disease, Chronic Obstructive , Child, Preschool , Ciliary Motility Disorders/genetics , Ciliary Motility Disorders/therapy , Genotype , HumansABSTRACT
Primary ciliary dyskinesia (PCD) is a rare genetic disease leading to bronchiectasis in most patients. In addition to the lungs, PCD might affect multiple organ systems, and patients frequently have multiple clinical problems, which require multidisciplinary management. Diagnosis of PCD needs a combination of tests, many of which require expertise and expensive equipment. Measurement of nasal nitric oxide is the first test to consider when PCD is suspected. Detailed clinical history using available predictive scores in combination with information on functional and structural aspects of lung disease is important to identify which patients should be referred for further diagnostic testing.
Subject(s)
Ciliary Motility Disorders , Nitric Oxide , Ciliary Motility Disorders/diagnosis , Ciliary Motility Disorders/therapy , HumansABSTRACT
Primary ciliary dyskinesia (PCD) is a rare genetic ciliopathy in which mucociliary clearance is disturbed by the abnormal motion of cilia or there is a severe reduction in the generation of multiple motile cilia. Lung damage ensues due to recurrent airway infections, sometimes even resulting in respiratory failure. So far, no causative treatment is available and treatment efforts are primarily aimed at improving mucociliary clearance and early treatment of bacterial airway infections. Treatment guidelines are largely based on cystic fibrosis (CF) guidelines, as few studies have been performed on PCD. In this review, we give a detailed overview of the clinical studies performed investigating PCD to date, including three trials and several case reports. In addition, we explore precision medicine approaches in PCD, including gene therapy, mRNA transcript and read-through therapy.
Subject(s)
Ciliary Motility Disorders , Bacterial Infections/genetics , Bacterial Infections/metabolism , Bacterial Infections/microbiology , Bacterial Infections/therapy , Ciliary Motility Disorders/genetics , Ciliary Motility Disorders/metabolism , Ciliary Motility Disorders/microbiology , Ciliary Motility Disorders/therapy , Clinical Trials as Topic , Cystic Fibrosis/genetics , Cystic Fibrosis/metabolism , Cystic Fibrosis/microbiology , Cystic Fibrosis/therapy , Humans , Lung/metabolism , Lung/microbiology , Respiratory Tract Infections/genetics , Respiratory Tract Infections/metabolism , Respiratory Tract Infections/microbiology , Respiratory Tract Infections/therapyABSTRACT
Introducción. Sobre la base de un caso clínico, se presenta la descripción del cuadro intersticial por disquinesia ciliar primaria de una paciente, desde los dos meses de edad (conforme el relato de la familia) hasta los 16 años, cumplidos en el año 2021. Método. Se realizó una evaluación clínica con extensos estudios para descartar otras patologías similares. El diagnóstico definitivo fue determinado por el estudio genético para disquinesia ciliar primaria (DQCP) y otros defectos genéticos informados por el laboratorio Ambrygen, Estados Unidos. Objetivos. Describir detalladamente la evolución de la paciente durante quince años, con énfasis en los estudios mencionados. Presentar la evolución desde el nacimiento hasta el año 2021 de una recién nacida con distress respiratorio (asistencia respiratoria mecánica durante diez días), con neumonía a los pocos días de nacer y con otitis, sinusitis y neumonías recurrentes, que llega a la fecha con una calidad de vida óptima, sin sinusitis, otitis ni neumonías y con espirometría normal. Su capacidad física para realizar cualquier actividad deportiva de esfuerzo importante señala la extraordinaria respuesta a los tratamientos. Presentar los hallazgos de genética, microscopía electrónica y estudios de barrido ciliar. Resultados. Confirmado su diagnóstico de DQCP, presentamos su seguimiento actualizado hasta el año 2021. La DQCP debe ser sospechada en recién nacidos y lactantes ante la persistencia de neumonías, otitis, sinusitis y bronquitis recurrentes. (AU)
Introduction. On the basis of a clinical case, a description of the interstitial picture due to primary ciliary dyskinesia of a patient from two months of age (according to the family's report) to 15 years of age, completed in the year 2021 is presented. Methodology. Clinical evaluation based on multiple studies to rule out another similar pathology. Final diagnosis was established through genetic studies for primary ciliary diskinesia (PCDK). (Ambrygen-USA). Objective. To describe clinical, laboratory and spirometric evolution of this patient during fifteen years. Also to bedescribe evolution since birth up to the year 2021. The patient was born with respiratory distress (needed mechanical ventilation for ten days), with pneumonia a few days after delivery, and with sinusitis and recurrent pneumonia. Finally, she has now a high quality of life. No sinusitis, otitis or pneumonia and normal spirometry. She´s able to perform heavy physical efforts. We present the genetic and electron microscopy (video) studies to observe ciliary beating. Results. After confirming your DQCP diagnosis, we present your updated follow-up until 2021. DQCP should be suspected in newborns and infants in the presence of recurrent pneumonia, otitis sinusitis and bronchitis. (AU)
Subject(s)
Humans , Female , Adolescent , Ciliary Motility Disorders/genetics , Lung Diseases, Interstitial , Follow-Up Studies , Ciliary Motility Disorders/diagnosis , Ciliary Motility Disorders/therapy , Diagnosis, DifferentialABSTRACT
BACKGROUND: Chest physiotherapy (CP) is a recommended treatment modality in primary ciliary dyskinesia (PCD). OBJECTIVE: Primary aim was to compare the efficacy and safety of the conventional chest physiotherapy (CCP) and oscillatory positive expiratory pressure therapy (OPEPT). Secondary aims were to compare the exacerbation rate, time until the first exacerbation, patient compliance and comfort between the two CP methods. METHODS: This is a 6 month randomized, controlled crossover trial. Patients >6 years of age with PCD were randomized into two groups, first group was assigned to OPEPT (Acapella®) for 3 months while second group was assigned to CCP. Groups were crossed over to the other modality after a 15-day washout period. Pulmonary function tests (PFTs) and compliance were monitored by monthly clinic visits. RESULTS: There was a significant increase in FEV1 , FEF25-75 , and PEF values (p = .018, p = .020, and p = .016, respectively) in the OPEPT group and in FVC values (p = .007) in CCP group compared to baseline. However PFT increase at 3rd month was not superior to each other with both physiotherapy methods. Median acute pulmonary exacerbation rate and time period until the first exacerbation were similar in both groups (p = .821, p = .092, respectively). Comfort and effectiveness of OPEPT was higher than CCP according to patients (p = .029 and p = .042, respectively). There were no adverse effects with either therapy. CONCLUSIONS: OPEPT was as effective as CCP in PCD patients. OPEPT was more comfortable and effective than CCP according to patients. OPEPT might be an efficient alternative method for airway cleareance in PCD patients.
Subject(s)
Ciliary Motility Disorders/therapy , Respiratory Therapy/methods , Adult , Ciliary Motility Disorders/physiopathology , Cross-Over Studies , Disease Progression , Female , Humans , Infant , Lung/physiopathology , Male , Middle Aged , Physical Therapy Modalities , Respiratory Function TestsABSTRACT
BACKGROUND Primary ciliary dyskinesia (PCD) is a disease characterized by motor ciliary dysfunction, which leads to the accumulation of secretions in the lower airways and, consequently, to atelectasis and repeated infections. During the neonatal period, diagnosis can be difficult because the symptoms are frequently associated with other respiratory diseases common in neonates. The laterality defects should warn the clinician of the need for further investigation using clinical criteria, but the confirmation depends on a genetic test. CASE REPORT The objective of this report is to present a case of PCD manifesting in the neonatal period that was diagnosed due to respiratory failure associated with recurrent atelectasis and situs inversus totalis. CONCLUSIONS This disease is not well known by neonatologists, but early diagnosis decreases morbidity and improves patient quality of life.
Subject(s)
Ciliary Motility Disorders/complications , Ciliary Motility Disorders/therapy , Pulmonary Atelectasis/etiology , Pulmonary Atelectasis/therapy , Respiratory Distress Syndrome, Newborn/etiology , Respiratory Distress Syndrome, Newborn/therapy , Administration, Inhalation , Continuous Positive Airway Pressure , Diagnosis, Differential , Humans , Infant, Newborn , Male , Situs InversusSubject(s)
Carrier Proteins/genetics , Ciliary Motility Disorders , Lung Diseases , Otitis , Situs Inversus , Child , Child, Preschool , Ciliary Motility Disorders/genetics , Ciliary Motility Disorders/physiopathology , Ciliary Motility Disorders/therapy , Diagnosis, Differential , Female , Hearing Loss/diagnosis , Hearing Loss/etiology , Humans , Loss of Function Mutation , Lung Diseases/diagnosis , Lung Diseases/etiology , Lung Diseases/physiopathology , Otitis/diagnosis , Otitis/etiology , Otitis/physiopathology , Patient Care Management , Siblings , Situs Inversus/diagnostic imaging , Situs Inversus/geneticsABSTRACT
OBJECTIVE: In England, the National Health Service commissioned a National Management Service for children with primary ciliary dyskinesia (PCD). The aims of this study were to describe the health of children seen in this Service and compare lung function to children with cystic fibrosis (CF). DESIGN: Multi-centre service evaluation of the English National Management PCD Service. SETTING: Four nationally commissioned PCD centres in England. PATIENTS: 333 children with PCD reviewed in the Service in 2015; lung function data were also compared with 2970 children with CF. RESULTS: Median age at diagnosis for PCD was 2.6 years, significantly lower in children with situs inversus (1.0 vs 6.0 years, p<0.001). Compared with national data from the CF Registry, mean (SD) %predicted forced expiratory volume in one second (FEV1) was 76.8% in PCD (n=240) and 85.0% in CF, and FEV1 was lower in children with PCD up to the age of 15 years. Approximately half of children had some hearing impairment, with 26% requiring hearing aids. Children with a lower body mass index (BMI) had lower FEV1 (p<0.001). One-third of children had positive respiratory cultures at review, 54% of these grew Haemophilus influenzae. CONCLUSIONS: We provide evidence that children with PCD in England have worse lung function than those with CF. Nutritional status should be considered in PCD management, as those with a lower BMI have significantly lower FEV1. Hearing impairment is common but seems to improve with age. Well-designed and powered randomised controlled trials on management of PCD are needed to inform best clinical practice.
Subject(s)
Ciliary Motility Disorders/diagnosis , Ciliary Motility Disorders/therapy , Child , Ciliary Motility Disorders/physiopathology , Combined Modality Therapy , Cystic Fibrosis/physiopathology , England , Female , Humans , Lung/physiopathology , Male , Respiratory Function Tests , State Medicine , Treatment OutcomeABSTRACT
Non-adherence to prescribed treatment is considered the foremost cause of treatment failure in chronic medical conditions. Airway clearance techniques (ACT) play a key role in the management of chronic suppurative lung disease yet, along with inhaled therapies such as nebulised antibiotics, adherence to these is often lower than to other treatments. In this review we discuss methods of monitoring adherence to these therapies and potential barriers and outline suggestions for improving adherence in the paediatric population.
Subject(s)
Bronchiectasis/therapy , Ciliary Motility Disorders/therapy , Cystic Fibrosis/therapy , Medication Adherence , Physical Therapy Modalities , Treatment Adherence and Compliance , Administration, Inhalation , Adolescent , Child , Child, Preschool , Humans , InfantABSTRACT
INTRODUCTION: Caregiver burden impacts both the social and economic framework of society. Cystic fibrosis (CF) causes significant caregiver burden, but the current data is scarce. In the case of primary ciliary dyskinesia (PCD), even less is known. This study aims to compare the caregiver burden of the parents of patients with CF and PCD. METHODS: Patients with CF and PCD between the ages of 6 to 13 and their parents were included. Patients' clinical information and parents' demographics were recorded. Caregiver burden was measured with Zarit Caregiver Burden Scale (ZCB), while the quality of life (QOL) was measured with CFQOL-revised (CFQOL-R) and PCD QOL questionnaire as the patients' age and diagnosis indicated. RESULTS: A total of 63 patients, 44 with CF (69%) and 85 caregivers (35 mothers, 6 fathers, and 22 mother-father dyads) participated in the study. Caregiver burden was significantly higher in mothers of the CF group with a mean ZCB of 30.5 ± 10.7 when compared to the PCD group with a mean ZCB of 21.93 ± 8.26 (P = .006). This was similar in fathers with mean ZCB of 27.5 ± 9.21 in the CF group and 20.36 ± 7.43 in the PCD group (P = .03). In correlation analyses, mothers' caregiver burden moderately and inversely correlated with CFQOL-R subscales in the CF population. CONCLUSION: Caregiver burden is significantly higher in the CF population when compared to PCD. It is correlated with pulmonary functions and QOL in patients with CF.
Subject(s)
Caregivers , Ciliary Motility Disorders/therapy , Cost of Illness , Cystic Fibrosis/therapy , Adaptation, Psychological , Adolescent , Adult , Child , Ciliary Motility Disorders/epidemiology , Cystic Fibrosis/epidemiology , Fathers , Female , Humans , Lung , Male , Mothers , Parents , Quality of Life , Surveys and QuestionnairesABSTRACT
Primary ciliary dyskinesia (PCD), also known as immotile-cilia syndrome, is a rare genetic disease that is inherited in an autosomal recessive manner. Several studies have explored certain aspects of PCD in the Arab world, yet much is still lacking in terms of identifying the different characteristics of this disease. In this paper, we aim to briefly cover those studies published about PCD in Arab countries, as well as to provide recommendations and guidelines for future studies.
Subject(s)
Ciliary Motility Disorders/ethnology , Arab World , Arabs/genetics , Ciliary Motility Disorders/diagnosis , Ciliary Motility Disorders/genetics , Ciliary Motility Disorders/therapy , Consanguinity , Humans , Kartagener Syndrome/diagnosis , Kartagener Syndrome/ethnology , Kartagener Syndrome/genetics , Kartagener Syndrome/therapy , Kuwait , Middle East , Practice Guidelines as Topic , Qatar , Research , Saudi Arabia , United Arab Emirates , YemenABSTRACT
Primary ciliary dyskinesia (PCD) is a rare and heterogeneous genetic disorder that affects the structure and function of motile cilia. In the airway epithelium, impaired ciliary motion results in reduced or absent mucociliary clearance that leads to the appearance of chronic airway infection, sinusitis, and bronchiectasis. Currently, there is no effective treatment for PCD, and research is limited by the lack of convenient models to study this disease and investigate innovative therapies. Furthermore, the high heterogeneity of PCD genotypes is likely to hinder the development of a single therapy for all patients. The generation of patient-derived, induced pluripotent stem cells, and their differentiation into airway epithelium, as well as genome editing technologies, could represent major tools for in vitro PCD modeling and for developing personalized therapies. Here, we review PCD pathogenesis and then discuss how human induced pluripotent stem cells could be used to model this disease for the development of innovative, patient-specific biotherapies.