Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
4.7
3.0
Journals
Diagnostics
Special Issues
Progress in Diagnosing and Managing Primary Ciliary Dyskinesia
share announcement

Progress in Diagnosing and Managing Primary Ciliary Dyskinesia

A special issue of Diagnostics (ISSN 2075-4418). This special issue belongs to the section "Pathology and Molecular Diagnostics".

Deadline for manuscript submissions: closed (31 July 2021) | Viewed by 34599

Special Issue Editor

Dr. Thomas Burgoyne

E-Mail Website
Guest Editor
1. UCL Institute of Ophthalmology, University College London, London, UK
2. Royal Brompton & Harefield NHS Trust, London, UK
Interests: repiratory disease and ophthalmology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Primary ciliary dyskinesia (PCD) is an inherited autosomal-recessive disorder of motile cilia that can result in severe multisystem, disease including chronic lung disease, rhinosinusitis, hearing impairment, and subfertility. An early and accurate diagnosis of PCD is vital to implement appropriate treatment aimed at preventing lung damage in childhood and preserving lung function. Confirmation of a diagnosis of PCD relies on a combination of tests, including measurement of nasal nitric oxide as well as acquiring cells by nasal brushings for examination of cilia motility using high-speed video microscopy, immunofluorescence microscopy, transmission electron microscopy, and genotyping. To date, there are >50 known PCD genes that have been identified, which reflects the complexity of the disease and challenges to reach a diagnosis. Research to advance the current testing methodology including greater genetic and phenotypic knowledge and introduction of new technologies has the potential to improve the accuracy and turnaround time of diagnosis and to enhance the management of PCD patients.

In this Special Issue, we are looking for original papers and reviews on the progress of diagnosing and managing PCD patients. This includes but is not limited to the following topics: (i) Advances in our understanding of genetic mutations that lead to PCD, (ii) imaging techniques examining mucociliary clearance as well as structure abnormalities or absence of axonemal components required for normal ciliary function, (iii) respiratory epithelial cell culture techniques, (iv) novel diagnostic procedures, and (v) innovative therapeutic approaches.

Dr. Thomas Burgoyne
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Diagnostics is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • cilia
  • mucociliary clearance
  • mucus
  • sputum
  • infection
  • genetics
  • cell culture
  • electron microscopy
  • immunofluorescence
  • high-speed video microscopy

Benefits of Publishing in a Special Issue

  • Ease of navigation: Grouping papers by topic helps scholars navigate broad scope journals more efficiently.
  • Greater discoverability: Special Issues support the reach and impact of scientific research. Articles in Special Issues are more discoverable and cited more frequently.
  • Expansion of research network: Special Issues facilitate connections among authors, fostering scientific collaborations.
  • External promotion: Articles in Special Issues are often promoted through the journal's social media, increasing their visibility.
  • e-Book format: Special Issues with more than 10 articles can be published as dedicated e-books, ensuring wide and rapid dissemination.

Further information on MDPI's Special Issue polices can be found here.

Published Papers (9 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Research

Jump to: Review

21 pages, 2447 KiB  
Article
A Comprehensive Approach for the Diagnosis of Primary Ciliary Dyskinesia—Experiences from the First 100 Patients of the PCD-UNIBE Diagnostic Center
by Loretta Müller, Sibel T. Savas, Stefan A. Tschanz, Andrea Stokes, Anaïs Escher, Mirjam Nussbaumer, Marina Bullo, Claudia E. Kuehni, Sylvain Blanchon, Andreas Jung, Nicolas Regamey, Beat Haenni, Martin Schneiter, Jonas Ingold, Elisabeth Kieninger, Carmen Casaulta, Philipp Latzin and on behalf of the Swiss PCD Research Group
Diagnostics 2021, 11(9), 1540; https://doi.org/10.3390/diagnostics11091540 - 25 Aug 2021
Cited by 8 | Viewed by 3466
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Progress in Diagnosing and Managing Primary Ciliary Dyskinesia)
►▼ Show Figures

Figure 1

12 pages, 2546 KiB  
Article
Quantitative Assessment of Ciliary Ultrastructure with the Use of Automatic Analysis: PCD Quant
by Andrea Felšöová, Tibor Sloboda, Lukáš Hudec, Miroslav Koblížek, Petr Pohunek, Vendula Martinů, Žofia Varényiová, Simona Kadlecová and Jiří Uhlík
Diagnostics 2021, 11(8), 1363; https://doi.org/10.3390/diagnostics11081363 - 29 Jul 2021
Cited by 1 | Viewed by 2284
Abstract
The ciliary ultrastructure can be damaged in various situations. Such changes include primary defects found in primary ciliary dyskinesia (PCD) and secondary defects developing in secondary ciliary dyskinesia (SCD). PCD is a genetic disease resulting from impaired ciliary motility causing chronic disease of [...] Read more.
The ciliary ultrastructure can be damaged in various situations. Such changes include primary defects found in primary ciliary dyskinesia (PCD) and secondary defects developing in secondary ciliary dyskinesia (SCD). PCD is a genetic disease resulting from impaired ciliary motility causing chronic disease of the respiratory tract. SCD is an acquired condition that can be caused, for example, by respiratory infection or exposure to tobacco smoke. The diagnosis of these diseases is a complex process with many diagnostic methods, including the evaluation of ciliary ultrastructure using transmission electron microscopy (the golden standard of examination). Our goal was to create a program capable of automatic quantitative analysis of the ciliary ultrastructure, determining the ratio of primary and secondary defects, as well as analysis of the mutual orientation of cilia in the ciliary border. PCD Quant, a program developed for the automatic quantitative analysis of cilia, cannot yet be used as a stand-alone method for evaluation and provides limited assistance in classifying primary and secondary defect classes and evaluating central pair angle deviations. Nevertheless, we see great potential for the future in automatic analysis of the ciliary ultrastructure. Full article
(This article belongs to the Special Issue Progress in Diagnosing and Managing Primary Ciliary Dyskinesia)
►▼ Show Figures

Figure 1

8 pages, 11703 KiB  
Article
High-Speed Video Microscopy for Primary Ciliary Dyskinesia Diagnosis: A Study of Ciliary Motility Variations with Time and Temperature
by Ana Reula, Javier Pitarch-Fabregat, Javier Milara, Julio Cortijo, Manuel Mata-Roig, Lara Milian and Miguel Armengot
Diagnostics 2021, 11(7), 1301; https://doi.org/10.3390/diagnostics11071301 - 20 Jul 2021
Cited by 8 | Viewed by 3206
Abstract
Primary ciliary dyskinesia (PCD) is a rare disease resulting from a defect in ciliary function that generates, among other issues, chronic upper and lower respiratory tract infections. European guidelines recommend studying ciliary function (pattern (CBP) and frequency (CBF)), together with characteristic clinical symptoms, [...] Read more.
Primary ciliary dyskinesia (PCD) is a rare disease resulting from a defect in ciliary function that generates, among other issues, chronic upper and lower respiratory tract infections. European guidelines recommend studying ciliary function (pattern (CBP) and frequency (CBF)), together with characteristic clinical symptoms, as one of the definitive tests. However, there is no “gold standard”. The present study aims to use high-speed video microscopy to describe how CBF and CBP alter over time and at different temperatures to reduce the error rate in the diagnosis of PCD. Samples of nasal epithelium from 27 healthy volunteers were studied to assess CBF and CBP at 0, 3, 24, 48, and 72 h, at room temperature and 4 °C. It was observed that CBF increased while CBP became dyskinetic, both at room temperature and at 4 °C, as time passed, especially after 3 h. In order to preserve all ciliary function parameters and to perform a reliable analysis to improve the diagnostic process of PCD, analysis should be performed within the first 3 h of sample collection, preferably in reference centers. Full article
(This article belongs to the Special Issue Progress in Diagnosing and Managing Primary Ciliary Dyskinesia)
►▼ Show Figures

Figure 1

10 pages, 879 KiB  
Article
Evaluation of a Clinical Index as a Predictive Tool for Primary Ciliary Dyskinesia
by Vendula Martinů, Lucie Bořek-Dohalská, Žofia Varényiová, Jiří Uhlík, Václav Čapek, Petr Pohunek and Václav Koucký
Diagnostics 2021, 11(6), 1088; https://doi.org/10.3390/diagnostics11061088 - 14 Jun 2021
Cited by 11 | Viewed by 2545
Abstract
Background: In primary ciliary dyskinesia (PCD) there is no single diagnostic test. Different predictive tools have been proposed to guide referral of high-risk patients for further diagnostic workup. We aimed to test clinical index (CI) on a large unselected cohort and compare its [...] Read more.
Background: In primary ciliary dyskinesia (PCD) there is no single diagnostic test. Different predictive tools have been proposed to guide referral of high-risk patients for further diagnostic workup. We aimed to test clinical index (CI) on a large unselected cohort and compare its characteristics with other widely used tools—PICADAR and NA-CDCF. Methods: CI, PICADAR, and NA-CDCF scores were calculated in 1401 patients with suspected PCD referred to our center. Their predictive characteristics were analyzed using receiver operating characteristics (ROC) curves and compared to each other. Nasal nitric oxide (nNO) was measured in 569 patients older than 3 years. Results: PCD was diagnosed in 67 (4.8%) patients. CI, PICADAR, and NA-CDCF scores were higher in PCD than in nonPCD group (all p < 0.001). The area under the ROC curve (AUC) for CI was larger than for NA-CDCF (p = 0.005); AUCPICADAR and AUCNA-CDCF did not differ (p = 0.093). An overlap in signs and symptoms among tools was identified. PICADAR could not be assessed in 86 (6.1%) patients without chronic wet cough. For CI laterality or congenital heart defects assessment was not necessary. nNO further improved predictive power of all three tools. Conclusion: CI is a feasible predictive tool for PCD that may outperform PICADAR and NA-CFCD. Full article
(This article belongs to the Special Issue Progress in Diagnosing and Managing Primary Ciliary Dyskinesia)
►▼ Show Figures

Figure 1

9 pages, 3766 KiB  
Article
UA-Zero as a Uranyl Acetate Replacement When Diagnosing Primary Ciliary Dyskinesia by Transmission Electron Microscopy
by Andreia Lucia Pinto, Ranjit Kaur Rai, Amelia Shoemark, Claire Hogg and Thomas Burgoyne
Diagnostics 2021, 11(6), 1063; https://doi.org/10.3390/diagnostics11061063 - 9 Jun 2021
Cited by 4 | Viewed by 3802
Abstract
Primary ciliary dyskinesia (PCD) is a disorder affecting motile cilia. An early accurate diagnosis helps prevent lung damage and preserve lung function. To make a diagnostic assessment, one of the commonly used methods that allows for the examination of ciliary ultrastructure is transmission [...] Read more.
Primary ciliary dyskinesia (PCD) is a disorder affecting motile cilia. An early accurate diagnosis helps prevent lung damage and preserve lung function. To make a diagnostic assessment, one of the commonly used methods that allows for the examination of ciliary ultrastructure is transmission electron microscopy (TEM). This allows for a quantitative assessment of ciliary components to identify defects associated with PCD. Heavy metal staining is required to provide a contrast when imaging cilia in the TEM. One of the most commonly used stains is uranyl acetate (UA). UA can be applied to cellular material before embedding (en bloc), or to ultrathin sections of embedded samples (grid staining). UA is radioactive and, due to growing safety concerns and restrictions by government bodies, universities and hospitals, it is essential to find a suitable alternative. We show UA-zero (UAZ), when used en bloc, provides a high contrast and is a suitable replacement for UA. PCD diagnostic experts, having reviewed ciliary cross-sections stained with UAZ en bloc, are confident that the staining and PCD defects are readily detectable similar to samples that have been stained with UA. Full article
(This article belongs to the Special Issue Progress in Diagnosing and Managing Primary Ciliary Dyskinesia)
►▼ Show Figures

Figure 1

12 pages, 1689 KiB  
Article
Primary Ciliary Dyskinesia Diagnostic Challenges: Understanding the Clinical Phenotype of the Puerto Rican RSPH4A Founder Mutation
by Wilfredo De Jesús-Rojas, Dalilah Reyes-De Jesús and Ricardo A. Mosquera
Diagnostics 2021, 11(2), 281; https://doi.org/10.3390/diagnostics11020281 - 11 Feb 2021
Cited by 14 | Viewed by 3335
Abstract
Primary ciliary dyskinesia (PCD) is a rare, heterogeneous ciliopathy resulting in chronic oto-sino-pulmonary disease, bronchiectasis, newborn respiratory distress, and laterality defects. PCD diagnosis can be achieved by following diagnostic algorithms that include electron microscopy, genetics, and ancillary testing. Genetic mutations in more than [...] Read more.
Primary ciliary dyskinesia (PCD) is a rare, heterogeneous ciliopathy resulting in chronic oto-sino-pulmonary disease, bronchiectasis, newborn respiratory distress, and laterality defects. PCD diagnosis can be achieved by following diagnostic algorithms that include electron microscopy, genetics, and ancillary testing. Genetic mutations in more than 45 genes, including RSPH4A, can lead to PCD. RSPH4A mutations located on chromosome six, affect radial spokes and results in central complex apparatus abnormalities. The RSPH4A [c.921 + 3_6delAAGT] founder mutation was described as one cause of PCD without laterality defects in Puerto Rico. Additionally, there are further diagnostic challenges present in the Puerto Rican population to diagnose PCD. We describe the demographics, clinical features, and RSPH4A genetic variants in 13 patients with clinical PCD affecting 11 Puerto Ricans from unrelated families. Full article
(This article belongs to the Special Issue Progress in Diagnosing and Managing Primary Ciliary Dyskinesia)
►▼ Show Figures

Figure 1

Review

Jump to: Research

9 pages, 278 KiB  
Review
Ciliary Videomicroscopy: A Long Beat from the European Respiratory Society Guidelines to the Recognition as a Confirmatory Test for Primary Ciliary Dyskinesia
by Noemie Bricmont, Mihaela Alexandru, Bruno Louis, Jean-François Papon and Céline Kempeneers
Diagnostics 2021, 11(9), 1700; https://doi.org/10.3390/diagnostics11091700 - 17 Sep 2021
Cited by 10 | Viewed by 2304
Abstract
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, [...] Read more.
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. Full article
(This article belongs to the Special Issue Progress in Diagnosing and Managing Primary Ciliary Dyskinesia)
15 pages, 1136 KiB  
Review
Diagnostics and Management of Male Infertility in Primary Ciliary Dyskinesia
by Channa N. Jayasena and Anu Sironen
Diagnostics 2021, 11(9), 1550; https://doi.org/10.3390/diagnostics11091550 - 26 Aug 2021
Cited by 20 | Viewed by 8097
Abstract
Primary ciliary dyskinesia (PCD), a disease caused by the malfunction of motile cilia, manifests mainly with chronic recurrent respiratory infections. In men, PCD is also often associated with infertility due to immotile sperm. Since causative mutations for PCD were identified in over 50 [...] Read more.
Primary ciliary dyskinesia (PCD), a disease caused by the malfunction of motile cilia, manifests mainly with chronic recurrent respiratory infections. In men, PCD is also often associated with infertility due to immotile sperm. Since causative mutations for PCD were identified in over 50 genes, the role of these genes in sperm development should be investigated in order to understand the effect of PCD mutations on male fertility. Previous studies showed that different dynein arm heavy chains are present in respiratory cilia and sperm flagellum, which may partially explain the variable effects of mutations on airways and fertility. Furthermore, recent studies showed that male reproductive tract motile cilia may play an important part in sperm maturation and transport. In some PCD patients, extremely low sperm counts were reported, which may be due to motile cilia dysfunction in the reproductive tract rather than problems with sperm development. However, the exact roles of PCD genes in male fertility require additional studies, as do the treatment options. In this review, we discuss the diagnostic and treatment options for men with PCD based on the current knowledge. Full article
(This article belongs to the Special Issue Progress in Diagnosing and Managing Primary Ciliary Dyskinesia)
►▼ Show Figures

Figure 1

12 pages, 1167 KiB  
Review
Progress in Diagnosing Primary Ciliary Dyskinesia: The North American Perspective
by Michael Glenn O’Connor, Amjad Horani and Adam J. Shapiro
Diagnostics 2021, 11(7), 1278; https://doi.org/10.3390/diagnostics11071278 - 16 Jul 2021
Cited by 24 | Viewed by 3710
Abstract
Primary Ciliary Dyskinesia (PCD) is a rare, under-recognized disease that affects respiratory ciliary function, resulting in chronic oto-sino-pulmonary disease. The PCD clinical phenotype overlaps with other common respiratory conditions and no single diagnostic test detects all forms of PCD. In 2018, PCD experts [...] Read more.
Primary Ciliary Dyskinesia (PCD) is a rare, under-recognized disease that affects respiratory ciliary function, resulting in chronic oto-sino-pulmonary disease. The PCD clinical phenotype overlaps with other common respiratory conditions and no single diagnostic test detects all forms of PCD. In 2018, PCD experts collaborated with the American Thoracic Society (ATS) to create a clinical diagnostic guideline for patients across North America, specifically considering the local resources and limitations for PCD diagnosis in the United States and Canada. Nasal nitric oxide (nNO) testing is recommended for first-line testing in patients ≥5 years old with a compatible clinical phenotype; however, all low nNO values require confirmation with genetic testing or ciliary electron micrograph (EM) analysis. Furthermore, these guidelines recognize that not all North American patients have access to nNO testing and isolated genetic testing is appropriate in cases with strong clinical PCD phenotypes. For unresolved diagnostic cases, referral to a PCD Foundation accredited center is recommended. The purpose of this narrative review is to provide insight on the North American PCD diagnostic process, to enhance the understanding of and adherence to current guidelines, and to promote collaboration with diagnostic pathways used outside of North America. Full article
(This article belongs to the Special Issue Progress in Diagnosing and Managing Primary Ciliary Dyskinesia)
►▼ Show Figures

Figure 1

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-9
Back to TopTop