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Respiratory Medicine Apr 2023Cystic fibrosis (CF) and Primary ciliary dyskinesia (PCD) are both rare chronic diseases, inherited disorders associated with multiple complications, namely respiratory... (Review)
Review
Cystic fibrosis (CF) and Primary ciliary dyskinesia (PCD) are both rare chronic diseases, inherited disorders associated with multiple complications, namely respiratory complications, due to impaired mucociliary clearance that affect severely patients' lives. Although both are classified as rare diseases, PCD has a much lower prevalence than CF, particularly among Caucasians. As a result, CF is well studied, better recognized by clinicians, and with some therapeutic approaches already available. Whereas PCD is still largely unknown, and thus the approach is based on consensus guidelines, expert opinion, and extrapolation from the larger evidence base available for patients with CF. Both diseases have some clinical similarities but are very different, necessitating different treatment by specialists who are familiar with the complexities of each disease.This review aims to provide an overview of the knowledge about the two diseases with a focus on the similarities and differences between both in terms of disease mechanisms, common clinical manifestations, genetics and the most relevant therapeutic options. We hoped to raise clinical awareness about PCD, what it is, how it differs from CF, and how much information is still lacking. Furthermore, this review emphasises the fact that both diseases require ongoing research to find better treatments and, in particular for PCD, to fill the medical and scientific gaps.
Topics: Humans; Cystic Fibrosis; Kartagener Syndrome; Chronic Disease; Prevalence
PubMed: 36828173
DOI: 10.1016/j.rmed.2023.107169 -
American Journal of Respiratory and... Jun 2018This document presents the American Thoracic Society clinical practice guidelines for the diagnosis of primary ciliary dyskinesia (PCD). (Meta-Analysis)
Meta-Analysis
BACKGROUND
This document presents the American Thoracic Society clinical practice guidelines for the diagnosis of primary ciliary dyskinesia (PCD).
TARGET AUDIENCE
Clinicians investigating adult and pediatric patients for possible PCD.
METHODS
Systematic reviews and, when appropriate, meta-analyses were conducted to summarize all available evidence pertinent to our clinical questions. Evidence was assessed using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach for diagnosis and discussed by a multidisciplinary panel with expertise in PCD. Predetermined conflict-of-interest management strategies were applied, and recommendations were formulated, written, and graded exclusively by the nonconflicted panelists. Three conflicted individuals were also prohibited from writing, editing, or providing feedback on the relevant sections of the manuscript.
RESULTS
After considering diagnostic test accuracy, confidence in the estimates for each diagnostic test, relative importance of test results studied, desirable and undesirable direct consequences of each diagnostic test, downstream consequences of each diagnostic test result, patient values and preferences, costs, feasibility, acceptability, and implications for health equity, the panel made recommendations for or against the use of specific diagnostic tests as compared with using the current reference standard (transmission electron microscopy and/or genetic testing) for the diagnosis of PCD.
CONCLUSIONS
The panel formulated and provided a rationale for the direction as well as for the strength of each recommendation to establish the diagnosis of PCD.
Topics: Cilia; Cohort Studies; Cross-Sectional Studies; Diagnostic Techniques and Procedures; Genetic Predisposition to Disease; Humans; Kartagener Syndrome; Practice Guidelines as Topic; Prospective Studies; Retrospective Studies; Sensitivity and Specificity; Societies, Medical; United States
PubMed: 29905515
DOI: 10.1164/rccm.201805-0819ST -
Advances in Experimental Medicine and... 2018Mutation of ZIC3 causes X-linked heterotaxy, a syndrome in which the laterality of internal organs is disrupted. Analysis of model organisms and gene expression during... (Review)
Review
Mutation of ZIC3 causes X-linked heterotaxy, a syndrome in which the laterality of internal organs is disrupted. Analysis of model organisms and gene expression during early development suggests ZIC3-related heterotaxy occurs due to defects at the earliest stage of left-right axis formation. Although there are data to support abnormalities of the node and cilia as underlying causes, it is unclear at the molecular level why loss of ZIC3 function causes such these defects. ZIC3 has putative roles in a number of developmental signalling pathways that have distinct roles in establishing the left-right axis. This complicates the understanding of the mechanistic basis of Zic3 in early development and left-right patterning. Here we summarise our current understanding of ZIC3 function and describe the potential role ZIC3 plays in important signalling pathways and their links to heterotaxy.
Topics: Animals; Dextrocardia; Genetic Diseases, X-Linked; Heterotaxy Syndrome; Homeodomain Proteins; Humans; Mutation; Signal Transduction; Transcription Factors
PubMed: 29442328
DOI: 10.1007/978-981-10-7311-3_15 -
Seminars in Respiratory and Critical... Apr 2015Primary ciliary dyskinesia (PCD) is an autosomal recessive disorder of cilia structure, function, and biogenesis leading to chronic infections of the respiratory tract,... (Review)
Review
Primary ciliary dyskinesia (PCD) is an autosomal recessive disorder of cilia structure, function, and biogenesis leading to chronic infections of the respiratory tract, fertility problems, and disorders of organ laterality. The diagnosis can be challenging, using traditional tools such as characteristic clinical features, ciliary function, and ultrastructural defects and newer screening tools such as nasal nitric oxide levels and genetic testing add to the diagnostic algorithm. There are 32 known PCD-causing genes, and in the future, comprehensive genetic testing may screen young infants before developing symptoms, thus improving survival. Therapies include surveillance of pulmonary function and microbiology, in addition to airway clearance, antibiotics, and early referral to bronchiectasis centers. As with cystic fibrosis (CF), standardized care at specialized centers using a multidisciplinary approach likely improves outcomes. In conjunction with the CF foundation, the PCD foundation, with experienced investigators and clinicians, is developing a network of PCD clinical centers to coordinate the effort in North America and Europe. As the network grows, clinical care and knowledge will improve.
Topics: Anti-Bacterial Agents; Anti-Inflammatory Agents; Cilia; Genetic Testing; Humans; Kartagener Syndrome; Microscopy, Electron, Transmission; Mutation; Nitric Oxide; Phenotype; Prognosis; Respiratory Function Tests
PubMed: 25826585
DOI: 10.1055/s-0035-1546748 -
Clinics in Chest Medicine Sep 2016Primary ciliary dyskinesia (PCD) is a recessive genetically heterogeneous disorder of motile cilia with chronic otosinopulmonary disease and organ laterality defects in... (Review)
Review
Primary ciliary dyskinesia (PCD) is a recessive genetically heterogeneous disorder of motile cilia with chronic otosinopulmonary disease and organ laterality defects in ∼50% of cases. The prevalence of PCD is difficult to determine. Recent diagnostic advances through measurement of nasal nitric oxide and genetic testing has allowed rigorous diagnoses and determination of a robust clinical phenotype, which includes neonatal respiratory distress, daily nasal congestion, and wet cough starting early in life, along with organ laterality defects. There is early onset of lung disease in PCD with abnormal airflow mechanics and radiographic abnormalities detected in infancy and early childhood.
Topics: Administration, Inhalation; Administration, Intranasal; Adrenal Cortex Hormones; Anti-Bacterial Agents; Breath Tests; Chronic Disease; Cilia; Cough; Endoscopy; Genetic Testing; Heterotaxy Syndrome; Humans; Kartagener Syndrome; Middle Ear Ventilation; Nasal Lavage; Nitric Oxide; Otitis Media; Phenotype; Respiratory Distress Syndrome, Newborn; Saline Solution, Hypertonic; Sinusitis; Situs Inversus
PubMed: 27514592
DOI: 10.1016/j.ccm.2016.04.008 -
The Canadian Veterinary Journal = La... Aug 2023. 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...
. 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 . 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 D Serge Messier).
Topics: Humans; Female; Dogs; Animals; Situs Inversus; Kartagener Syndrome; Heart Septal Defects, Ventricular; Tomography, X-Ray Computed; Dog Diseases
PubMed: 37529390
DOI: No ID Found -
Annals of the American Thoracic Society Apr 2023
Topics: Humans; Child; Kartagener Syndrome; Ciliary Motility Disorders; Respiration Disorders; Genotype; Mucus
PubMed: 37000147
DOI: 10.1513/AnnalsATS.202301-021ED -
The Pan African Medical Journal 2018
Topics: Adult; Cough; Dextrocardia; Humans; Kartagener Syndrome; Male; Pneumonia; Sinusitis
PubMed: 30050624
DOI: 10.11604/pamj.2018.29.160.14927 -
Orphanet Journal of Rare Diseases Jul 2022Primary ciliary dyskinesia (PCD) represents a highly heterogenous disorder with extensive clinical and genetic patterns among populations of different geographic... (Review)
Review
BACKGROUND
Primary ciliary dyskinesia (PCD) represents a highly heterogenous disorder with extensive clinical and genetic patterns among populations of different geographic location and ethnic origin. However, data about Chinese patients are limited. We aimed to summarize the clinical and genetic spectrum of Chinese PCD patients based on all available literatures.
METHODS
We searched Embase, Pubmed, Web of Science and Chinese databases including CNKI, SinoMed and Wanfang from 1981 to 2021, to identify articles reporting patients with PCD in China, which had included information about transmission electron microscopy and/or genetic testing.
RESULTS
A total of 244 Chinese PCD patients in 52 articles were included. Of these patients, the mean age was 13.1 years, and 55 patients (22.5%) were diagnosed with PCD after 18 years old. Compared with patients diagnosed with PCD in childhood or infancy, patients diagnosed with PCD in adulthood had a higher prevalence of chronic wet cough, sinusitis, Pseudomonas aeruginosa (PA) isolation and radiological bronchiectasis as well as worse lung function. 25 PCD-related genes were identified in 142 patients, and DNAH5, DNAH11, CCDC39 and CCDC40 were the most frequently detected mutations. More than half of genetic variants were loss-of-function mutations, and the majority of these variants were seen only once. Correlations between PCD phenotype, genotype and ciliary ultrastructure were also evidenced.
CONCLUSIONS
Diagnostic delay and under-recognition of PCD remain a big issue in China, which contributes to progressive lung disease and PA infection indicating worse outcome. Specialist equipment and expertise are urgently required to facilitate the early diagnosis and treatment of PCD.
TRIAL REGISTRY
PROSPERO; No.: CRD42021257804; URL: www.crd.york.ac.uk/prospero/.
Topics: Cilia; Ciliary Motility Disorders; Delayed Diagnosis; Genotype; Humans; Kartagener Syndrome; Mutation; Phenotype
PubMed: 35854386
DOI: 10.1186/s13023-022-02427-1 -
Zhong Nan Da Xue Xue Bao. Yi Xue Ban =... Jan 2022Primary ciliary dyskinesia (PCD) is a hereditary disease characterized by airway mucociliary clearance dysfunction. The estimated prevalence of PCD is 1꞉10 000 to...
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.
Topics: Chronic Disease; Cilia; Humans; Kartagener Syndrome; Phenotype; Sinusitis
PubMed: 35545371
DOI: 10.11817/j.issn.1672-7347.2022.210379