scholarly journals European Respiratory Society guidelines for the diagnosis of primary ciliary dyskinesia

2016 ◽  
Vol 49 (1) ◽  
pp. 1601090 ◽  
Author(s):  
Jane S. Lucas ◽  
Angelo Barbato ◽  
Samuel A. Collins ◽  
Myrofora Goutaki ◽  
Laura Behan ◽  
...  
Keyword(s):  
Diagnostic Tests ◽  
Primary Ciliary Dyskinesia ◽  
High Speed ◽  
Task Force ◽  
Clinical Care ◽  
Beat Frequency ◽  
Diagnostic Methods ◽  
Future Research ◽  
European Respiratory Society ◽  
Ciliary Dyskinesia

The diagnosis of primary ciliary dyskinesia is often confirmed with standard, albeit complex and expensive, tests. In many cases, however, the diagnosis remains difficult despite the array of sophisticated diagnostic tests. There is no “gold standard” reference test. Hence, a Task Force supported by the European Respiratory Society has developed this guideline to provide evidence-based recommendations on diagnostic testing, especially in light of new developments in such tests, and the need for robust diagnoses of patients who might enter randomised controlled trials of treatments. The guideline is based on pre-defined questions relevant for clinical care, a systematic review of the literature, and assessment of the evidence using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach. It focuses on clinical presentation, nasal nitric oxide, analysis of ciliary beat frequency and pattern by high-speed video-microscopy analysis, transmission electron microscopy, genotyping and immunofluorescence. It then used a modified Delphi survey to develop an algorithm for the use of diagnostic tests to definitively confirm and exclude the diagnosis of primary ciliary dyskinesia; and to provide advice when the diagnosis was not conclusive. Finally, this guideline proposes a set of quality criteria for future research on the validity of diagnostic methods for primary ciliary dyskinesia.

scholarly journals New Diagnostic Methods and Treatment Recommendations in Primary Ciliary Dyskinesia

2020 ◽  
pp. 42-49
Author(s):  
Nagihan Emiralioğlu
Keyword(s):  
Diagnostic Tests ◽  
Primary Ciliary Dyskinesia ◽  
High Speed ◽  
Electron Tomography ◽  
Diagnostic Methods ◽  
European Respiratory Society ◽  
Transmission Electron ◽  
Nutritional Advice ◽  
Organ Laterality ◽  
Ciliary Dyskinesia

Primary ciliary dyskinesia (PCD) is a rare and genetically heterogeneous disease and clinically characterized by neonatal respiratory distress, organ laterality defects, persistent rhinosinusitis, chronic bronchitis, and eventually bronchiectasis. Currently, there is no single “gold standard” diagnostic test for PCD. PICADAR (Primary Ciliary Dyskinesia Rule) score is a guide to decide for further evaluation of diagnostic tests in PCD. European Respiratory Society (ERS) and American Thoracic Society (ATS) recommend diagnostic tests, including nasal nitric oxide (nNO), high-speed video analysis (HSVMA), transmission electron microscopy (TEM) and genetic testing. Cryo-electron tomography and immunofluorescence methods are new techniques recently performed by specialized centers and needs to be improved. Age at diagnosis for PCD changes according to awareness of disease and available diagnostic tests in different centers. Regular follow-up and multidisciplinary approach is important in the management of PCD. The main aim of the treatment is to prevent pulmonary exacerbations and slow the progression of the disease since there are no treatment approaches to correct the underlying cilia structure and its functions in PCD. Although, there are not enough randomized controlled trials for the treatment of PCD, recent treatments are usually based on to improve the mucociliary clearance. Early diagnosis with multidisciplinary management and nutritional advice could improve growth and delay disease progression leading to bronchiectasis and lung function impairment in PCD

scholarly journals Diagnosis of primary ciliary dyskinesia: summary of the ERS Task Force report

Breathe ◽  
2017 ◽  
Vol 13 (3) ◽  
pp. 166-178 ◽  
Author(s):  
Claudia E. Kuehni ◽  
Jane S. Lucas
Keyword(s):  
Secondary Care ◽  
Primary Ciliary Dyskinesia ◽  
High Speed ◽  
Task Force ◽  
Diagnostic Testing ◽  
List Type ◽  
European Respiratory Society ◽  
Term Infants ◽  
Task Force Report ◽  
Ciliary Dyskinesia

Key pointsPrimary ciliary dyskinesia (PCD) is a genetically and clinically heterogeneous disease characterised by abnormal motile ciliary function.There is no “gold standard” diagnostic test for PCD.The European Respiratory Society (ERS) Task Force Guidelines for diagnosing PCD recommend that patients should be referred for diagnostic testing if they have several of the following features: persistent wet cough; situs anomalies; congenital cardiac defects; persistent rhinitis; chronic middle ear disease with or without hearing loss; or a history, in term infants, of neonatal upper and lower respiratory symptoms or neonatal intensive care admission.The ERS Task Force recommends that patients should be investigated in a specialist PCD centre with access to a range of complementary tests: nasal nitric oxide, high-speed video microscopy analysis and transmission electron microscopy. Additional tests including immunofluorescence labelling of ciliary proteins and genetic testing may also help determine the diagnosis.Educational aimsThis article is intended for primary and secondary care physicians interested in primary ciliary dyskinesia (PCD), i.e. those who identify patients for testing, and those involved in diagnosing and managing PCD patients. It aims: to inform readers about the new European Respiratory Society Task Force Guidelines for diagnosing patients with PCDto enable primary and secondary care physicians to: identify patients who need diagnostic testing; understand the diagnostic tests that their patients will undergo, the results of the tests and their limitations; and ensure that appropriate care is subsequently delivered.

scholarly journals Deep phenotyping, including quantitative ciliary beating parameters, and extensive genotyping in primary ciliary dyskinesia

2019 ◽  
Vol 57 (4) ◽  
pp. 237-244 ◽  
Author(s):  
Sylvain Blanchon ◽  
Marie Legendre ◽  
Mathieu Bottier ◽  
Aline Tamalet ◽  
Guy Montantin ◽  
...  
Keyword(s):  
Primary Ciliary Dyskinesia ◽  
High Speed ◽  
Genetic Disorder ◽  
Beat Frequency ◽  
Ciliary Beat Frequency ◽  
Central Complex ◽  
Ciliary Beating ◽  
Recovery Stroke ◽  
Biallelic Mutations ◽  
Ciliary Dyskinesia

BackgroundPrimary ciliary dyskinesia (PCD) is a rare genetic disorder resulting in abnormal ciliary motility/structure, extremely heterogeneous at genetic and ultrastructural levels. We aimed, in light of extensive genotyping, to identify specific and quantitative ciliary beating anomalies, according to the ultrastructural phenotype.MethodsWe prospectively included 75 patients with PCD exhibiting the main five ultrastructural phenotypes (n=15/group), screened all corresponding PCD genes and measured quantitative beating parameters by high-speed video-microscopy (HSV).ResultsSixty-eight (91%) patients carried biallelic mutations. Combined outer/inner dynein arms (ODA/IDA) defect induces total ciliary immotility, regardless of the gene involved. ODA defect induces a residual beating with dramatically low ciliary beat frequency (CBF) related to increased recovery stroke and pause durations, especially in case of DNAI1 mutations. IDA defect with microtubular disorganisation induces a low percentage of beating cilia with decreased beating angle and, in case of CCDC39 mutations, a relatively conserved mean CBF with a high maximal CBF. Central complex defect induces nearly normal beating parameters, regardless of the gene involved, and a gyrating motion in a minority of ciliated edges, especially in case of RSPH1 mutations. PCD with normal ultrastructure exhibits heterogeneous HSV values, but mostly an increased CBF with an extremely high maximal CBF.ConclusionQuantitative HSV analysis in PCD objectives beating anomalies associated with specific ciliary ultrastructures and genotypes. It represents a promising approach to guide the molecular analyses towards the best candidate gene(s) to be analysed or to assess the pathogenicity of the numerous sequence variants identified by next-generation-sequencing.

scholarly journals CiliarMove: new software for evaluating ciliary beat frequency helps find novel mutations by a Portuguese multidisciplinary team on primary ciliary dyskinesia

2021 ◽  
Vol 7 (1) ◽  
pp. 00792-2020
Author(s):  
Pedro Sampaio ◽  
Mónica Ferro da Silva ◽  
Inês Vale ◽  
Mónica Roxo-Rosa ◽  
Andreia Pinto ◽  
...  
Keyword(s):  
Healthy Volunteers ◽  
Open Source ◽  
Primary Ciliary Dyskinesia ◽  
High Speed ◽  
Beat Frequency ◽  
Ciliary Beat Frequency ◽  
Control Group ◽  
Observation Method ◽  
Ciliary Dyskinesia ◽  
Ciliary Beat

Evaluation of ciliary beat frequency (CBF) performed by high-speed videomicroscopy analysis (HVMA) is one of the techniques required for the correct diagnosis of primary ciliary dyskinesia (PCD). Currently, due to lack of open-source software, this technique is widely performed by visually counting the ciliary beatings per a given time-window. Our aim was to generate open-source, fast and intuitive software for evaluating CBF, validated in Portuguese PCD patients and healthy volunteers.Nasal brushings collected from 17 adult healthy volunteers and 34 PCD-referred subjects were recorded using HVMA. Evaluation of CBF was compared by two different methodologies: the new semi-automated computer software CiliarMove and the manual observation method using slow-motion movies. Clinical history, nasal nitric oxide and transmission electron microscopy were performed for diagnosis of PCD in the patient group. Genetic analysis was performed in a subset (n=8) of suspected PCD patients.The correlation coefficient between the two methods was R2=0.9895. The interval of CBF values obtained from the healthy control group (n=17) was 6.18–9.17 Hz at 25°C. In the PCD-excluded group (n=16), CBF ranged from 6.84 to 10.93 Hz and in the PCD group (n=18), CBF ranged from 0 to 14.30 Hz.We offer an automated open-source programme named CiliarMove, validated by the manual observation method in a healthy volunteer control group, a PCD-excluded group and a PCD-confirmed group. In our hands, comparisons between CBF intervals alone could discern between healthy and PCD groups in 78% of the cases.

scholarly journals Diagnosis of primary ciliary dyskinesia: potential options for resource-limited countries

2017 ◽  
Vol 26 (143) ◽  
pp. 160058 ◽  
Author(s):  
Nisreen Rumman ◽  
Claire Jackson ◽  
Samuel Collins ◽  
Patricia Goggin ◽  
Janice Coles ◽  
...  
Keyword(s):  
Diagnostic Tests ◽  
Primary Ciliary Dyskinesia ◽  
High Speed ◽  
Care Setting ◽  
Nasal Nitric Oxide ◽  
Ciliary Function ◽  
Resource Limited ◽  
Transmission Electron ◽  
Sophisticated Equipment ◽  
Ciliary Dyskinesia

Primary ciliary dyskinesia is a genetic disease of ciliary function leading to chronic upper and lower respiratory tract symptoms. The diagnosis is frequently overlooked because the symptoms are nonspecific and the knowledge about the disease in the primary care setting is poor. Additionally, none of the available tests is accurate enough to be used in isolation. These tests are expensive, and need sophisticated equipment and expertise to analyse and interpret results; diagnosis is therefore only available at highly specialised centres. The diagnosis is particularly challenging in countries with limited resources due to the lack of such costly equipment and expertise.In this review, we discuss the importance of early and accurate diagnosis especially for countries where the disease is clinically prevalent but diagnostic tests are lacking. We review the diagnostic tests available in specialised centres (nasal nitric oxide, high-speed video microscopy, transmission electron microscopy, immunofluorescence and genetics). We then consider modifications that might be considered in less well-resourced countries whilst maintaining acceptable accuracy.

scholarly journals Ciliary beat pattern and frequency in genetic variants of primary ciliary dyskinesia

2014 ◽  
Vol 44 (6) ◽  
pp. 1579-1588 ◽  
Author(s):  
Johanna Raidt ◽  
Julia Wallmeier ◽  
Rim Hjeij ◽  
Jörg Große Onnebrink ◽  
Petra Pennekamp ◽  
...  
Keyword(s):  
Primary Ciliary Dyskinesia ◽  
High Speed ◽  
Genetic Disorder ◽  
Beat Frequency ◽  
Detailed Knowledge ◽  
Beat Pattern ◽  
Biallelic Mutations ◽  
Tract Infections ◽  
Ciliary Dyskinesia ◽  
Ciliary Beat

Primary ciliary dyskinesia (PCD) is a rare genetic disorder leading to recurrent respiratory tract infections. High-speed video-microscopy analysis (HVMA) of ciliary beating, currently the first-line diagnostic tool for PCD in most centres, is challenging because recent studies have expanded the spectrum of HVMA findings in PCD from grossly abnormal to very subtle. The objective of this study was to describe the diversity of HVMA findings in genetically confirmed PCD individuals.HVMA was performed as part of the routine work-up of individuals with suspected PCD. Subsequent molecular analysis identified biallelic mutations in the PCD-related genes of 66 individuals. 1072 videos of these subjects were assessed for correlation with the genotype.Biallelic mutations (19 novel) were found in 17 genes: DNAI1, DNAI2, DNAH5, DNAH11, CCDC103, ARMC4, KTU/DNAAF2, LRRC50/DNAAF1, LRRC6, DYX1C1, ZMYND10, CCDC39, CCDC40, CCDC164, HYDIN, RSPH4A and RSPH1. Ciliary beat pattern variations correlated well with the genetic findings, allowing the classification of typical HVMA findings for different genetic groups. In contrast, analysis of ciliary beat frequency did not result in additional diagnostic impact.In conclusion, this study provides detailed knowledge about the diversity of HVMA findings in PCD and may therefore be seen as a guide to the improvement of PCD diagnostics.

scholarly journals Ciliary Videomicroscopy: A Long Beat from the European Respiratory Society Guidelines to the Recognition as a Confirmatory Test for Primary Ciliary Dyskinesia

Diagnostics ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 1700
Author(s):  
Noemie Bricmont ◽  
Mihaela Alexandru ◽  
Bruno Louis ◽  
Jean-François Papon ◽  
Céline Kempeneers
Keyword(s):  
Primary Ciliary Dyskinesia ◽  
High Speed ◽  
Diagnostic Algorithm ◽  
Automated Analysis ◽  
Confirmatory Test ◽  
European Respiratory Society ◽  
Specific Test ◽  
Gold Standard Method ◽  
No Gold Standard ◽  
Ciliary Dyskinesia

Primary ciliary dyskinesia (PCD) is a rare inherited ciliopathy in which respiratory cilia are stationary or dyskinetic. The clinical presentation of PCD is highly non-specific since it includes infections and disorders of the upper (otitis and rhinosinusitis) and lower (neonatal respiratory distress, bronchitis, pneumonia and bronchiectasis) airways, starting in early life. Clinical examination alone does not allow a PCD diagnosis, which relies on several concordant tests, since none are sensitive or specific enough alone. Despite being the most sensitive and specific test to diagnose PCD, digital high-speed videomicroscopy (DHSV) is not sufficiently standardized, preventing its use with complete confidence as a confirmatory diagnostic test for PCD, or its inclusion in a diagnostic algorithm. Since the 2017 ERS recommendations for PCD diagnosis, three main issues remain to be solved in order to optimize DHSV ciliary beating evaluation: the problem in defining an accurate sensitivity and specificity as there is no gold standard method to diagnose all PCD cases, a lack of standardization in the operating procedure for processing respiratory samples, and in the choice of measured parameters (self-operating or not). The development of new automated analysis approaches is promising and will require full clinical validation.

scholarly journals Diagnosing primary ciliary dyskinesia: an international patient perspective

2016 ◽  
Vol 48 (4) ◽  
pp. 1096-1107 ◽  
Author(s):  
Laura Behan ◽  
Audrey Dunn Galvin ◽  
Bruna Rubbo ◽  
Sarah Masefield ◽  
Fiona Copeland ◽  
...  
Keyword(s):  
Primary Ciliary Dyskinesia ◽  
Task Force ◽  
Past History ◽  
Genetic Disorder ◽  
Diagnostic Testing ◽  
Delayed Diagnosis ◽  
Patient Survey ◽  
European Respiratory Society ◽  
Medical Practitioners ◽  
Ciliary Dyskinesia

Primary ciliary dyskinesia (PCD) is a rare genetic disorder characterised by progressive sino-pulmonary disease, with symptoms starting soon after birth. A European Respiratory Society (ERS) Task Force aims to address disparities in diagnostics across Europe by providing evidence-based clinical practice guidelines. We aimed to identify challenges faced by patients when referred for PCD diagnostic testing.A patient survey was developed by patient representatives and healthcare specialists to capture experience. Online versions of the survey were translated into nine languages and completed in 25 countries. Of the respondents (n=365), 74% were PCD-positive, 5% PCD-negative and 21% PCD-uncertain/inconclusive. We then interviewed 20 parents/patients. Transcripts were analysed thematically.35% of respondents visited their doctor more than 40 times with PCD-related symptoms prior to diagnostic referral. Furthermore, the most prominent theme among interviewees was a lack of PCD awareness among medical practitioners and failure to take past history into account, leading to delayed diagnosis. Patients also highlighted the need for improved reporting of results and a solution to the “inconclusive” diagnostic status.These findings will be used to advise the ERS Task Force guidelines for diagnosing PCD, and should help stakeholders responsible for improving existing services and expanding provision for diagnosis of this rare disease.

scholarly journals A European Respiratory Society technical standard: exhaled biomarkers in lung disease

2017 ◽  
Vol 49 (4) ◽  
pp. 1600965 ◽  
Author(s):  
Ildiko Horváth ◽  
Peter J. Barnes ◽  
Stelios Loukides ◽  
Peter J. Sterk ◽  
Marieann Högman ◽  
...  
Keyword(s):  
Task Force ◽  
Exhaled Breath Condensate ◽  
Research Priorities ◽  
Disease Diagnosis ◽  
Future Research ◽  
Exhaled Breath ◽  
Sample Collection ◽  
European Respiratory Society ◽  
Technical Standards ◽  
Breath Tests

Breath tests cover the fraction of nitric oxide in expired gas (FENO), volatile organic compounds (VOCs), variables in exhaled breath condensate (EBC) and other measurements. For EBC and for FENO, official recommendations for standardised procedures are more than 10 years old and there is none for exhaled VOCs and particles. The aim of this document is to provide technical standards and recommendations for sample collection and analytic approaches and to highlight future research priorities in the field. For EBC and FENO, new developments and advances in technology have been evaluated in the current document. This report is not intended to provide clinical guidance on disease diagnosis and management.Clinicians and researchers with expertise in exhaled biomarkers were invited to participate. Published studies regarding methodology of breath tests were selected, discussed and evaluated in a consensus-based manner by the Task Force members.Recommendations for standardisation of sampling, analysing and reporting of data and suggestions for research to cover gaps in the evidence have been created and summarised.Application of breath biomarker measurement in a standardised manner will provide comparable results, thereby facilitating the potential use of these biomarkers in clinical practice.

scholarly journals Pcdp1 is a central apparatus protein that binds Ca2+-calmodulin and regulates ciliary motility

2010 ◽  
Vol 189 (3) ◽  
pp. 601-612 ◽  
Author(s):  
Christen G. DiPetrillo ◽  
Elizabeth F. Smith
Keyword(s):  
Primary Ciliary Dyskinesia ◽  
Calcium Concentration ◽  
Beat Frequency ◽  
Calcium Sensor ◽  
Central Pair ◽  
Ciliary Motility ◽  
Significant Impairment ◽  
Central Apparatus ◽  
Cilia And Flagella ◽  
Ciliary Dyskinesia

For all motile eukaryotic cilia and flagella, beating is regulated by changes in intraciliary calcium concentration. Although the mechanism for calcium regulation is not understood, numerous studies have shown that calmodulin (CaM) is a key axonemal calcium sensor. Using anti-CaM antibodies and Chlamydomonas reinhardtii axonemal extracts, we precipitated a complex that includes four polypeptides and that specifically interacts with CaM in high [Ca2+]. One of the complex members, FAP221, is an orthologue of mammalian Pcdp1 (primary ciliary dyskinesia protein 1). Both FAP221 and mammalian Pcdp1 specifically bind CaM in high [Ca2+]. Reduced expression of Pcdp1 complex members in C. reinhardtii results in failure of the C1d central pair projection to assemble and significant impairment of motility including uncoordinated bends, severely reduced beat frequency, and altered waveforms. These combined results reveal that the central pair Pcdp1 (FAP221) complex is essential for control of ciliary motility.

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