Primary ciliary dyskinesia in Japan: systematic review and meta-analysis.
Ontology highlight
ABSTRACT: Background
Primary ciliary dyskinesia (PCD) is a rare genetic disorder. Although the genetic tests and new diagnostic algorithms have recently been recommended, clinical signs and electron microscope (EM) findings have historically been the mainstays of diagnosis in Asia. To characterize PCD previously reported in Japan, we conducted a systematic review and meta-analysis.Methods
A search using MEDLINE, EMBASE, and Japana Centra Revuo Medicina (in Japanese) databases was carried out to identify articles reporting PCD, Kartagener syndrome, or immotile cilia syndrome in Japanese patients and published between 1985 and 2015.Results
After excluding duplication from 334 reports, we extracted 316 patients according to the criteria. Diagnosis was most frequently made in adulthood (148 patients [46.8%]???18?years old, 24 patients [7.6%]?ConclusionDelayed diagnosis of this congenital disease with high frequency of IDA defects and low frequency of ODA defects appear to be historical features of PCD reported in Japan, when EM was a main diagnostic tool. This review highlights problems experienced in this field, and provides basic information to establish a modernized PCD diagnosis and management system in the future.
SUBMITTER: Inaba A
PROVIDER: S-EPMC6659197 | biostudies-literature | 2019 Jul
REPOSITORIES: biostudies-literature
Publications
Primary ciliary dyskinesia in Japan: systematic review and meta-analysis.
Inaba Atsushi A Furuhata Masanori M Morimoto Kozo K Rahman Mahbubur M Takahashi Osamu O Hijikata Minako M Knowles Michael R MR Keicho Naoto N
BMC pulmonary medicine 20190725 1
<h4>Background</h4>Primary ciliary dyskinesia (PCD) is a rare genetic disorder. Although the genetic tests and new diagnostic algorithms have recently been recommended, clinical signs and electron microscope (EM) findings have historically been the mainstays of diagnosis in Asia. To characterize PCD previously reported in Japan, we conducted a systematic review and meta-analysis.<h4>Methods</h4>A search using MEDLINE, EMBASE, and Japana Centra Revuo Medicina (in Japanese) databases was carried o ...[more]
Similar Datasets
Project description:Primary ciliary dyskinesia (PCD) is a genetic, heterogeneous disease caused by dysfunction of cilia. Evidence is sparse and reports of lung function in PCD patients range from normal to severe impairment. This systematic review and meta-analysis of studies of lung function in PCD patients examines the spirometric indices of PCD patients and differences by age group and sex. We searched PubMed, Embase and Scopus for studies that described lung function in 10 or more patients with PCD. We performed meta-analyses and meta-regression to explain heterogeneity. We included 24 studies, ranging from 13 to 158 patients per study. The most commonly reported spirometric indices were forced expiratory volume in 1 s (FEV1) and forced vital capacity presented as mean and standard deviation of percent predicted values. We found considerable heterogeneity for both parameters (I2=94-96%). The heterogeneity remained when we stratified the analysis by age; however, FEV1 in adult patients was lower. Even after taking into account explanatory factors, the largest part of the between-studies variance remained unexplained. Heterogeneity could be explained by genetic differences between study populations, methodological factors related to the variability of study inclusion criteria or details on the performance and evaluation of lung function measurements that we could not account for. Prospective studies therefore need to use standardised protocols and international reference values. These results underline the possibility of distinct PCD phenotypes as in other chronic respiratory diseases. Detailed characterisation of these phenotypes and related genotypes is needed in order to better understand the natural history of PCD.
| S-EPMC6513038 | biostudies-literature
Project description:Primary ciliary dyskinesia (PCD) is a rare genetic disorder characterised by progressive sinopulmonary disease, with symptoms starting soon after birth. The aim of this study is to critically review, analyse, and synthesise the literature in order to understand the experiences of patients with primary ciliary dyskinesia (PCD) and the impact on health-related quality of life.MEDLINE, EBSCO, Cumulative Index to Nursing and Allied Health Literature (CINAHL), PsycINFO and EMBASE were searched according to the inclusion criteria. A qualitative analysis of 14 studies was conducted.Fourteen studies were included in the review, five with qualitative methodologies. Studies originated from the UK, USA, Italy, Denmark and Belgium, one study included a survey distributed internationally. Significant relationships were found between age and worsening of respiratory symptoms, physical, and mental domains of health-related quality of life, with a greater decline compared with reference populations. Variations between the UK and Italy were found for health-related quality of life and its correlation with time since diagnosis. PCD was found to have a physical impact in all age groups: patients found it difficult to keep up with others, and found energy levels were easily depleted compared to family or peers. In terms of social impact, symptoms lead to embarrassment and a sense of isolation, with patients concealing symptoms and/or their diagnosis. In turn, isolation was also linked with the lack of public and medical knowledge. In relation to emotional impact, anxiety was reported in a number of qualitative studies; patients were anxious about getting sick or when thinking about their future health. The burden of treatment and factors influencing adherence were also discussed in depth.Health-related quality of life decreases with age in patients with PCD. For all age groups, PCD was found to greatly impact physical, emotional, social functioning, and treatment burden. More research is needed on the psychosocial impact of the illness, disease burden and its effect on quality of life.
| S-EPMC5548843 | biostudies-other
Project description:RATIONALE:Primary ciliary dyskinesia (PCD) is a rare disorder causing chronic otosinopulmonary disease, generally diagnosed through evaluation of respiratory ciliary ultrastructure and/or genetic testing. Nasal nitric oxide (nNO) measurement is used as a PCD screening test because patients with PCD have low nNO levels, but its value as a diagnostic test remains unknown. OBJECTIVES:To perform a systematic review to assess the utility of nNO measurement (index test) as a diagnostic tool compared with the reference standard of electron microscopy (EM) evaluation of ciliary defects and/or detection of biallelic mutations in PCD genes. DATA SOURCES:Ten databases were searched for reference sources from database inception through July 29, 2016. DATA EXTRACTION:Study inclusion was limited to publications with rigorous nNO index testing, reference standard diagnostic testing with EM and/or genetics, and calculable diagnostic accuracy information for cooperative patients (generally >5 yr old) with high suspicion of PCD. SYNTHESIS:Meta-analysis provided a summary estimate for sensitivity and specificity and a hierarchical summary receiver operating characteristic curve. The Quality Assessment of Diagnostic Accuracy Studies-2 tool was used to assess study quality, and Grading of Recommendations Assessment, Development, and Evaluation was used to assess the certainty of evidence. In 12 study populations (1,344 patients comprising 514 with PCD and 830 without PCD), using a reference standard of EM alone or EM and/or genetic testing, summary sensitivity was 97.6% (92.7-99.2) and specificity was 96.0% (87.9-98.7), with a positive likelihood ratio of 24.3 (7.6-76.9), a negative likelihood ratio of 0.03 (0.01-0.08), and a diagnostic odds ratio of 956.8 (141.2-6481.5) for nNO measurements. After studies using EM alone as the reference standard were excluded, the seven studies using an extended reference standard of EM and/or genetic testing showed a summary sensitivity of nNO measurements of 96.3% (88.7-98.9) and specificity of 96.4% (85.1-99.2), with a positive likelihood ratio of 26.5 (5.9-119.1), a negative likelihood ratio of 0.04 (0.01-0.12), and a diagnostic odds ratio of 699.3 (67.4-7256.0). Certainty of the evidence was graded as moderate. CONCLUSIONS:nNO is a sensitive and specific test for PCD in cooperative patients (generally >5 yr old) with high clinical suspicion for this disease. With a moderate level of evidence, this meta-analysis confirms that nNO testing using velum closure maneuvers has diagnostic accuracy similar to EM and/or genetic testing for PCD when cystic fibrosis is ruled out. Thus, low nNO values accompanied by an appropriate clinical phenotype could be used as a diagnostic PCD test, though EM and/or genetics will continue to provide confirmatory information.
| S-EPMC6137897 | biostudies-other
Project description: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.
| S-EPMC4873960 | biostudies-literature
Project description:BackgroundPrimary 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.MethodsWe 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.ResultsA 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.ConclusionsDiagnostic 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 registryPROSPERO; No.: CRD42021257804; URL: www.crd.york.ac.uk/prospero/.
| S-EPMC9295413 | biostudies-literature
Project description:BackgroundA correlation exists between the microbial flora of the upper and lower airways in patients with cystic fibrosis (CF) or with primary ciliary dyskinesia (PCD). The sinuses can function as a bacterial reservoir where gram-negative bacteria adapt to the airways and repeatedly are aspirated to and colonize the lungs according to the theory of the united (unified) airways. Whereas the pattern of bacterial flora in the lower airways has been extensively studied, the upper airways have drawn limited attention.ObjectiveOur aim was to review the literature that reported bacterial flora in the sinuses and nasal cavities of patients with CF or PCD.MethodsA number of medical literature data bases were systematically searched between January 1960 and July 2016. We applied the following inclusion criteria: a minimum of one case of PCD (or Kartagener syndrome) or CF, and microbiology analyses from the nose or paranasal sinuses.ResultsWe included 46 studies (1823 patients) from 16 countries. Staphylococcus aureus was found in 30% of the noses and sinuses of patients with CF. Other common bacteria found included Pseudomonas aeruginosa, coagulase negative staphylococci, and Haemophilus influenzae. In PCD, H. influenzae was the most common bacteria (28%), followed by Streptococcus pneumoniae and P. aeruginosa. If studies that included nonsurgical swab and blowing samples were excluded, then P. aeruginosa was the most common bacterium in patients with CF (34%) and in patients with PCD (50%), followed by S. aureus and H. influenza.ConclusionS. aureus, P. aeruginosa, coagulase negative staphylococci, and H. influenzae dominated in the upper airways of patients with CF. In patients with PCD, H. influenzae, S. pneumoniae, and P. aeruginosa dominated. When studies that included swab and blowing samples were excluded, P. aeruginosa was the most common bacterium in both groups. Direct comparisons among the studies were restricted due to very heterogeneous methods, and a better standardization of procedures and outcomes is needed.
| S-EPMC5590177 | biostudies-literature
Project description:BackgroundPrimary ciliary dyskinesia (PCD) is a rare congenital respiratory disorder characterized by abnormal ciliary motility leading to chronic airway infections. Qualitative evaluation of ciliary beat pattern based on digital high-speed videomicroscopy analysis has been proposed in the diagnosis process of PCD. Although this evaluation is easy in typical cases, it becomes difficult when ciliary beating is partially maintained. We postulated that a quantitative analysis of beat pattern would improve PCD diagnosis. We compared quantitative parameters with the qualitative evaluation of ciliary beat pattern in patients in whom the diagnosis of PCD was confirmed or excluded.MethodsNasal nitric oxide measurement, nasal brushings and biopsies were performed prospectively in 34 patients with suspected PCD. In combination with qualitative analysis, 12 quantitative parameters of ciliary beat pattern were determined on high-speed videomicroscopy recordings of beating ciliated edges. The combination of ciliary ultrastructural abnormalities on transmission electron microscopy analysis with low nasal nitric oxide levels was the "gold standard" used to establish the diagnosis of PCD.ResultsThis "gold standard" excluded PCD in 15 patients (non-PCD patients), confirmed PCD in 10 patients (PCD patients) and was inconclusive in 9 patients. Among the 12 parameters, the distance traveled by the cilium tip weighted by the percentage of beating ciliated edges presented 96% sensitivity and 95% specificity. Qualitative evaluation and quantitative analysis were concordant in non-PCD patients. In 9/10 PCD patients, quantitative analysis was concordant with the "gold standard", while the qualitative evaluation was discordant with the "gold standard" in 3/10 cases. Among the patients with an inconclusive "gold standard", the use of quantitative parameters supported PCD diagnosis in 4/9 patients (confirmed by the identification of disease-causing mutations in one patient) and PCD exclusion in 2/9 patients.ConclusionsWhen the beat pattern is normal or virtually immotile, the qualitative evaluation is adequate to study ciliary beating in patients suspected for PCD. However, when cilia are still beating but with moderate alterations (more than 40% of patients suspected for PCD), quantitative analysis is required to precise the diagnosis and can be proposed to select patients eligible for TEM.
| S-EPMC3562218 | biostudies-literature
Project description:Primary Ciliary Dyskinesia (PCD, MIM 242650) is a rare, hereditary multiorgan disease characterized by malfunction of motile cilia. Hallmark symptom is a chronic airway infection due to mucostasis leading to irreversible lung damage that may progress to respiratory failure. There is no cure for this genetic disease and evidence-based treatment is limited. Until recently, there were no randomized controlled trials performed in PCD, but this year, data of the first placebo-controlled trial on pharmacotherapy in PCD were published. This cornerstone in the management of PCD was decisive for reviewing currently used treatment strategies. This article is a consensus of patient representatives and clinicians, which are highly experienced in care of PCD-patients and provides an overview of the management of PCD. Treatments are mainly based on expert opinions, personal experiences, or are deduced from other lung diseases, notably cystic fibrosis (CF), COPD or bronchiectasis. Most strategies focus on routine airway clearance and treatment of recurrent respiratory tract infections. Non-respiratory symptoms are treated organ specific. To generate further evidence-based knowledge, other projects are under way, e.?g. the International PCD-Registry. Participating in patient registries facilitates access to clinical and research studies and strengthens networks between centers. In addition, knowledge of genotype-specific course of the disease will offer the opportunity to further improve and individualize patient care.
| S-EPMC7671756 | biostudies-literature
Project description:We performed whole genome gene expression profiling in bronchial biopsies from PCD patients. We used the Quality Threshold clustering algorithm to identify groups of genes that revealed highly correlated RNA expression patterns in the biopsies. The largest cluster contained 372 genes and was significantly enriched for genes related to cilia. The database and literature search showed that 16250 genes in this cluster were known cilia genes, strongly indicating that the remaining 21022 genes were likely to be new cilia genes. The tissue expression pattern of the 210 new cilia genes and the 162 known genes was consistent with the presence of motile cilia in a given tissue. Analysis of the upstream promotor sequences revealed evidence for RFX transcription factors binding site motif in both subgroups. Total RNA obtained from 6 primary ciliary dyskinesia patients and 9 control individuals
2015-02-24 | E-GEOD-25186 | biostudies-arrayexpress
Project description:We performed whole genome gene expression profiling in bronchial biopsies from PCD patients. We used the Quality Threshold clustering algorithm to identify groups of genes that revealed highly correlated RNA expression patterns in the biopsies. The largest cluster contained 372 genes and was significantly enriched for genes related to cilia. The database and literature search showed that 16250 genes in this cluster were known cilia genes, strongly indicating that the remaining 21022 genes were likely to be new cilia genes. The tissue expression pattern of the 210 new cilia genes and the 162 known genes was consistent with the presence of motile cilia in a given tissue. Analysis of the upstream promotor sequences revealed evidence for RFX transcription factors binding site motif in both subgroups.
2015-02-24 | GSE25186 | GEO