scholarly journals Chronic Lung Disease in Canadian Aboriginal Children Is Not Caused by Abnormal Cilia

1997 ◽  
Vol 4 (4) ◽  
pp. 211-214 ◽  
Author(s):  
Bruce K Rubin ◽  
Vijay Kumar
Keyword(s):  
New Zealand ◽  
Primary Ciliary Dyskinesia ◽  
Congenital Defects ◽  
Recurrent Pneumonia ◽  
Northern Ontario ◽  
Transmission Electron ◽  
Aboriginal Children ◽  
Nasal Cilia ◽  
Abnormal Cilia ◽  
Ciliary Dyskinesia

BACKGROUND: It has been suggested that abnormalities of the airway cilia are responsible for some of the increased prevalence of bronchiectasis among the Polynesian population of New Zealand.OBJECTIVE: To determine whether abnormalities of the ciliary axoneme were present in Cree children with recurrent pneumonia.DESIGN: Retrospective identification of Cree children under 18 years of age with three or more documented episodes of pneumonia, at least one of which was severe enough to require hospitalization. Physical examination and nasal brushing for ciliary ultrastructure were performed on those who consented to participate in the study.SETTING: Out-patient department of Moose Factory General Hospital, the referral hospital for the James Bay Region of Northern Ontario.PATIENTS: Ten children (seven males; three females) met the diagnostic criteria and lived in Moose Factory or Moosonee. Six patients (five boys, one girl, mean age 7 years 2 months) consented to examination and nasal brushing.RESULTS: Although the percentage of abnormal cilia (21%) was three to seven times greater than that reported for the control population, the abnormalities seen were characteristic of acquired axonemal defects rather than primary ciliary dyskinesia.CONCLUSIONS: In this population, recurrent pneumonia did not appear to be associated with congenital defects of the ciliary axoneme (primary ciliary dyskinesia). This is consistent with a review of published transmission electron microscopy studies of nasal cilia from the Maori of New Zealand.

scholarly journals Primary ciliary dyskinesia with normal ultrastructure: three-dimensional tomography detects absence of DNAH11

2018 ◽  
Vol 51 (2) ◽  
pp. 1701809 ◽  
Author(s):  
Amelia Shoemark ◽  
Thomas Burgoyne ◽  
Robert Kwan ◽  
Mellisa Dixon ◽  
Mitali P. Patel ◽  
...  
Keyword(s):  
Primary Ciliary Dyskinesia ◽  
Electron Tomography ◽  
Three Dimensional ◽  
Structural Abnormality ◽  
Healthy Controls ◽  
Ultrastructural Studies ◽  
Transmission Electron ◽  
Causal Variants ◽  
Diagnostic Samples ◽  
Ciliary Dyskinesia

In primary ciliary dyskinesia (PCD), motile ciliary dysfunction arises from ciliary defects usually confirmed by transmission electron microscopy (TEM). In 30% of patients, such as those with DNAH11 mutations, apparently normal ultrastructure makes diagnosis difficult. Genetic analysis supports diagnosis, but may not identify definitive causal variants. Electron tomography, an extension of TEM, produces three-dimensional ultrastructural ciliary models with superior resolution to TEM. Our hypothesis is that tomography using existing patient samples will enable visualisation of DNAH11-associated ultrastructural defects. Dual axis tomograms from araldite-embedded nasal cilia were collected in 13 PCD patients with normal ultrastructure (DNAH11 n=7, HYDIN n=2, CCDC65 n=3 and DRC1 n=1) and six healthy controls, then analysed using IMOD and Chimera software.DNAH11 protein is localised to the proximal ciliary region. Within this region, electron tomography indicated a deficiency of >25% of proximal outer dynein arm volume in all patients with DNAH11 mutations (n=7) compared to other patients with PCD and normal ultrastructure (n=6) and healthy controls (n=6). DNAH11 mutations cause a shared abnormality in ciliary ultrastructure previously undetectable by TEM. Advantageously, electron tomography can be used on existing diagnostic samples and establishes a structural abnormality where ultrastructural studies were previously normal.

scholarly journals Immunofluorescence Analysis as a Diagnostic Tool in a Spanish Cohort of Patients with Suspected Primary Ciliary Dyskinesia

2020 ◽  
Vol 9 (11) ◽  
pp. 3603
Author(s):  
Noelia Baz-Redón ◽  
Sandra Rovira-Amigo ◽  
Mónica Fernández-Cancio ◽  
Silvia Castillo-Corullón ◽  
Maria Cols ◽  
...  
Keyword(s):  
Diagnostic Tool ◽  
Primary Ciliary Dyskinesia ◽  
Low Cost ◽  
Immunofluorescence Analysis ◽  
Transmission Electron Microscopy Analysis ◽  
Transmission Electron ◽  
Electron Microscopy Analysis ◽  
Diagnosis Rate ◽  
Microscopy Analysis ◽  
Ciliary Dyskinesia

Primary ciliary dyskinesia (PCD) is an autosomal recessive rare disease caused by an alteration of ciliary structure. Immunofluorescence, consisting in the detection of the presence and distribution of cilia proteins in human respiratory cells by fluorescence, has been recently proposed as a technique to improve understanding of disease-causing genes and diagnosis rate in PCD. The objective of this study is to determine the accuracy of a panel of four fluorescently labeled antibodies (DNAH5, DNALI1, GAS8 and RSPH4A or RSPH9) as a PCD diagnostic tool in the absence of transmission electron microscopy analysis. The panel was tested in nasal brushing samples of 74 patients with clinical suspicion of PCD. Sixty-eight (91.9%) patients were evaluable for all tested antibodies. Thirty-three cases (44.6%) presented an absence or mislocation of protein in the ciliary axoneme (15 absent and 3 proximal distribution of DNAH5 in the ciliary axoneme, 3 absent DNAH5 and DNALI1, 7 absent DNALI1 and cytoplasmatic localization of GAS8, 1 absent GAS8, 3 absent RSPH9 and 1 absent RSPH4A). Fifteen patients had confirmed or highly likely PCD but normal immunofluorescence results (68.8% sensitivity and 100% specificity). In conclusion, immunofluorescence analysis is a quick, available, low-cost and reliable diagnostic test for PCD, although it cannot be used as a standalone test.

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 Frequency and Types of Ciliary Ultrastructural Defects in Patients With Suspected Primary Ciliary Dyskinesia Symptoms Analyzed by Transmission Electron Microscopy

2021 ◽  
Author(s):  
Mitra Rezaei ◽  
Amirali Soheili ◽  
Atefeh Fakharian ◽  
Hamid Jamaati ◽  
Jahangir Ghorbani ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Transmission Electron Microscopy ◽  
Primary Ciliary Dyskinesia ◽  
Respiratory Infections ◽  
Descriptive Analysis ◽  
Final Diagnosis ◽  
International Consensus ◽  
Tem Analysis ◽  
Transmission Electron ◽  
Ciliary Dyskinesia

Abstract Background: Primary ciliary dyskinesia (PCD) is a rare autosomal recessive condition of often chronic respiratory infections in early life. A useful tool for early diagnosis of such ciliary abnormalities is transmission electron microscopy (TEM). This study aimed to use TEM to examine these defects and speculate on a diagnosis.Methods: From 2017 to 2019, all referral patients with suspected PCD symptoms were included in this study. Nasal samples were taken after exclusion of further potential differential diagnosis and prepared for TEM. The final diagnosis was based on the International Consensus Guideline for reporting transmission electron microscopy results in the diagnosis of PCD. A descriptive analysis of demographic and ciliary ultrastructural data was performed by SPSS ver 21.Results: Study population consisted of 37 women and 30 men (mean age=20.34±10.7 years). The clinical presentations were as follows: bronchiectasis: 26 patients (38.8%); sinusitis: 23(34.3%); recurrent respiratory infection: 21 patients (31.3%); auditory symptoms: 5 patients (7.5%); situs inversus: 3 patients (4.4%); productive cough: 2 patients (3%); infertility: 2 patients (3%); polyposis: 1 patient (1.5%). According to TEM analysis, 12 (17%) of patients were PCD, 11 (15.7%) were indicating PCD cases, 26 (37.1%) of them had no criteria of PCD and 18 (25.7%) of cases had normal ciliary ultrastructure. Compound cilia and extra-tubule were reported in 29 (41.4%) and 31(44.3%) of patients, respectively. The outer dynein arm defect was seen in 11(16.4%) cases and the inner dynein arm (IDA) defect was seen in 20 (29.8%) cases. Two patients (3%) had microtubular disorganization.Conclusion: Bronchiectasis and sinusitis were the most common complications. The compound cilia and extra-tubule were the most prevalent TEM finding among all participants. However, the most prevalent hallmark diagnostic defects among PCD patients were ODA and IDA defects among PCD patients. Other diagnostic PCD tests should also be performed in patients in the indicating PCD group, those without PCD criteria, and normal patients with a highly suggestive history. Cell-culture, as well, should confirm IDA defects. This study highlights the fundamental need to consider ciliary defect among probable diagnoses and use TEM as a practical diagnostic tool.

scholarly journals Ciliary Feature Counter: A program for the Quantitative Assessment of Cilia to Diagnose Primary Ciliary Dyskinesia

Diagnostics ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. 524
Author(s):  
Andreia L. Pinto ◽  
Ranjit K. Rai ◽  
Claire Hogg ◽  
Thomas Burgoyne
Keyword(s):  
Electron Microscopy ◽  
Transmission Electron Microscopy ◽  
Primary Ciliary Dyskinesia ◽  
Quantitative Assessment ◽  
Consensus Guideline ◽  
International Consensus ◽  
Transmission Electron ◽  
Speed Up ◽  
Ciliary Dyskinesia ◽  
Ciliary Ultrastructure

Primary ciliary dyskinesia (PCD) is a disorder that affects motile cilia in the airway that are required for the removal of mucus, debris, and pathogens. It is important to diagnose PCD in early childhood to preserve lung function. The confirmation of a diagnosis relies on the assessment of ciliary ultrastructure by transmission electron microscopy (TEM). TEM involves the quantitative assessment of the ciliary ultrastructure to identify PCD defects as well as abnormalities resulting from infection. Many specialist diagnostic centres still rely on physical counters to tally results and paper notes to summarise findings before transferring the results to computer databases/records. To speed up the diagnostic data collection and increase the protection of patient information, we have developed digital ciliary feature counters that conform to the PCD reporting international consensus guideline. These counters can be used on a computer or tablet, and automatically generate notes regarding sample observations. We show that the digital counters are easy to use and can generate TEM diagnostic reports that will be useful for many PCD diagnostic centres.

scholarly journals Olfactory dysfunction is worse in primary ciliary dyskinesia compared with other causes of chronic sinusitis in children

Thorax ◽  
2018 ◽  
Vol 73 (10) ◽  
pp. 980-982 ◽  
Author(s):  
Massimo Pifferi ◽  
Andrew Bush ◽  
Michele Rizzo ◽  
Alessandro Tonacci ◽  
Maria Di Cicco ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Primary Ciliary Dyskinesia ◽  
Chronic Sinusitis ◽  
Olfactory Dysfunction ◽  
Healthy Controls ◽  
Sinus Disease ◽  
Multiple Functions ◽  
Nasal Nitric Oxide ◽  
Transmission Electron ◽  
Ciliary Dyskinesia

Cilia have multiple functions including olfaction. We hypothesised that olfactory function could be impaired in primary ciliary dyskinesia (PCD). Olfaction, nasal nitric oxide (nNO) and sinus CT were assessed in patients with PCD and non-PCD sinus disease, and healthy controls (no CT scan). PCD and non-PCD patients had similar severity of sinus disease. Despite this, defective olfaction was more common in patients with PCD (P<0.0001) and more severe in patients with PCD with major Transmission Electron Microscopy (TEM) abnormalities. Only in classical PCD did olfaction inversely correlate with sinusitis and nNO. We speculate that defective olfaction in PCD is primary in nature.

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