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 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 Diagnosis of Primary Ciliary Dyskinesia: Discrepancy according to different algorithms

2021 ◽  
pp. 00353-2021
Author(s):  
Mirjam Nussbaumer ◽  
Elisabeth Kieninger ◽  
Stefan A. Tschanz ◽  
Sibel T Savas ◽  
Carmen Casaulta ◽  
...  
Keyword(s):  
Primary Ciliary Dyskinesia ◽  
Diagnostic Algorithm ◽  
Final Diagnosis ◽  
Standard Test ◽  
Considerable Proportion ◽  
Evidence Based ◽  
Gold Standard Test ◽  
No Gold Standard ◽  
Ciliary Dyskinesia ◽  
Diagnostic Centre

BackgroundDiagnosis of primary ciliary dyskinesia (PCD) is challenging since there is no gold standard test. The European Respiratory (ERS) and American Thoracic (ATS) Societies developed evidence-based diagnostic guidelines with considerable differences.ObjectiveWe aimed to compare the algorithms published by the ERS and the ATS with each other and with our own PCD-UNIBE algorithm in a clinical setting. Our algorithm is similar to the ERS algorithm with additional immunofluorescence staining. Agreement (Cohen's kappa) and concordance between the three algorithms were assessed in patients with suspicion of PCD referred to our diagnostic centre.ResultsIn 46 out of 54 patients (85%) the final diagnosis was concordant between all three algorithms (30 PCD negative, 16 PCD positive). In eight patients (15%) PCD diagnosis differed between the algorithms. Five patients (9%) were diagnosed as PCD only by the ATS, one (2%) only by the ERS and PCD-UNIBE, one (2%) only by the ATS and PCD-UNIBE, and one (2%) only by the PCD-UNIBE algorithm. Agreement was substantial between the ERS and the ATS (κ=0.72, 95% Confidence Interval (CI) 0.53–0.92) and the ATS and the PCD-UNIBE (κ=0.73, CI 0.53–0.92) and almost perfect between the ERS and the PCD-UNIBE algorithms (κ=0.92, CI 0.80–1.00).ConclusionThe different diagnostic algorithms lead to a contradictory diagnosis in a considerable proportion of patients. Thus, an updated, internationally harmonized and standardised PCD diagnostic algorithm is needed to improve diagnostics for these discordant cases.

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 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 A Revised Protocol for Culture of Airway Epithelial Cells as a Diagnostic Tool for Primary Ciliary Dyskinesia

2020 ◽  
Vol 9 (11) ◽  
pp. 3753
Author(s):  
Janice L. Coles ◽  
James Thompson ◽  
Katie L. Horton ◽  
Robert A. Hirst ◽  
Paul Griffin ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Primary Ciliary Dyskinesia ◽  
High Speed ◽  
Ex Vivo ◽  
Cell Damage ◽  
Airway Epithelial Cells ◽  
University Hospital ◽  
Mitigation Measures ◽  
Diagnostic Certainty ◽  
Ciliary Dyskinesia

Air–liquid interface (ALI) culture of nasal epithelial cells is a valuable tool in the diagnosis and research of primary ciliary dyskinesia (PCD). Ex vivo samples often display secondary dyskinesia from cell damage during sampling, infection or inflammation confounding PCD diagnostic results. ALI culture enables regeneration of healthy cilia facilitating differentiation of primary from secondary ciliary dyskinesia. We describe a revised ALI culture method adopted from April 2018 across three collaborating PCD diagnostic sites, including current University Hospital Southampton COVID-19 risk mitigation measures, and present results. Two hundred and forty nasal epithelial cell samples were seeded for ALI culture and 199 (82.9%) were ciliated. Fifty-four of 83 (63.9%) ex vivo samples which were originally equivocal or insufficient provided diagnostic information following in vitro culture. Surplus basal epithelial cells from 181 nasal brushing samples were frozen in liquid nitrogen; 39 samples were ALI-cultured after cryostorage and all ciliated. The ciliary beat patterns of ex vivo samples (by high-speed video microscopy) were recapitulated, scanning electron microscopy demonstrated excellent ciliation, and cilia could be immuno-fluorescently labelled (anti-alpha-tubulin and anti-RSPH4a) in representative cases that were ALI-cultured after cryostorage. In summary, our ALI culture protocol provides high ciliation rates across three centres, minimising patient recall for repeat brushing biopsies and improving diagnostic certainty. Cryostorage of surplus diagnostic samples was successful, facilitating PCD research.

A decision analysis approach for the development of an evidence based diagnostic algorithm for Primary Ciliary Dyskinesia

2017 ◽  
Author(s):  
Panayiotis Kouis ◽  
Stefania I. Papatheodorou ◽  
Nicos Middleton ◽  
Kyriacos Kyriacou ◽  
John S. Evans ◽  
...  
Keyword(s):  
Decision Analysis ◽  
Primary Ciliary Dyskinesia ◽  
Diagnostic Algorithm ◽  
Analysis Approach ◽  
Evidence Based ◽  
Ciliary Dyskinesia

scholarly journals Accuracy of diagnostic testing in primary ciliary dyskinesia

2015 ◽  
Vol 47 (3) ◽  
pp. 837-848 ◽  
Author(s):  
Claire L. Jackson ◽  
Laura Behan ◽  
Samuel A. Collins ◽  
Patricia M. Goggin ◽  
Elizabeth C. Adam ◽  
...  
Keyword(s):  
Sensitivity And Specificity ◽  
Primary Ciliary Dyskinesia ◽  
High Speed ◽  
Diagnostic Testing ◽  
Standard Test ◽  
Diagnostic Process ◽  
Published Data ◽  
Transmission Electron ◽  
Repeated Sampling ◽  
Ciliary Dyskinesia

Diagnosis of primary ciliary dyskinesia (PCD) lacks a “gold standard” test and is therefore based on combinations of tests including nasal nitric oxide (nNO), high-speed video microscopy analysis (HSVMA), genotyping and transmission electron microscopy (TEM). There are few published data on the accuracy of this approach.Using prospectively collected data from 654 consecutive patients referred for PCD diagnostics we calculated sensitivity and specificity for individual and combination testing strategies. Not all patients underwent all tests.HSVMA had excellent sensitivity and specificity (100% and 93%, respectively). TEM was 100% specific, but 21% of PCD patients had normal ultrastructure. nNO (30 nL·min−1 cut-off) had good sensitivity and specificity (91% and 96%, respectively). Simultaneous testing using HSVMA and TEM was 100% sensitive and 92% specific.In conclusion, combination testing was found to be a highly accurate approach for diagnosing PCD. HSVMA alone has excellent accuracy, but requires significant expertise, and repeated sampling or cell culture is often needed. TEM alone is specific but misses 21% of cases. nNO (≤30 nL·min−1) contributes well to the diagnostic process. In isolation nNO screening at this cut-off would miss ∼10% of cases, but in combination with HSVMA could reduce unnecessary further testing. Standardisation of testing between centres is a future priority.

scholarly journals A Comprehensive Approach for the Diagnosis of Primary Ciliary Dyskinesia—Experiences from the First 100 Patients of the PCD-UNIBE Diagnostic Center

Diagnostics ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 1540
Author(s):  
Loretta Müller ◽  
Sibel T. Savas ◽  
Stefan A. Tschanz ◽  
Andrea Stokes ◽  
Anaïs Escher ◽  
...  
Keyword(s):  
Cell Culture ◽  
Cell Cultures ◽  
Primary Ciliary Dyskinesia ◽  
High Speed ◽  
Comprehensive Approach ◽  
Structural Proteins ◽  
Diagnostic Center ◽  
Immunofluorescence Labeling ◽  
Ciliary Dyskinesia ◽  
Ciliary Ultrastructure

Primary ciliary dyskinesia (PCD) is a rare genetic disease characterized by dyskinetic cilia. Respiratory symptoms usually start at birth. The lack of diagnostic gold standard tests is challenging, as PCD diagnostics requires different methods with high expertise. We founded PCD-UNIBE as the first comprehensive PCD diagnostic center in Switzerland. Our diagnostic approach includes nasal brushing and cell culture with analysis of ciliary motility via high-speed-videomicroscopy (HSVM) and immunofluorescence labeling (IF) of structural proteins. Selected patients undergo electron microscopy (TEM) of ciliary ultrastructure and genetics. We report here on the first 100 patients assessed by PCD-UNIBE. All patients received HSVM fresh, IF, and cell culture (success rate of 90%). We repeated the HSVM with cell cultures and conducted TEM in 30 patients and genetics in 31 patients. Results from cell cultures were much clearer compared to fresh samples. For 80 patients, we found no evidence of PCD, 17 were diagnosed with PCD, two remained inconclusive, and one case is ongoing. HSVM was diagnostic in 12, IF in 14, TEM in five and genetics in 11 cases. None of the methods was able to diagnose all 17 PCD cases, highlighting that a comprehensive approach is essential for an accurate diagnosis of PCD.

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