Primary Ciliary Dyskinesia Workup

Updated: Oct 17, 2017
  • Author: Girish D Sharma, MD, FCCP, FAAP; Chief Editor: Denise Serebrisky, MD  more...
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Workup

Laboratory Studies

Genetic Testing

Thirty-three disease-causing mutations have been identified [22] . All but two of these follow autosomal recessive inheritance. Eighteen of these are associated with outer dynein arm defect and nine also involve inner dynein arm defects. Nineteen of these mutations are included in the commercial PCD genetic testing panel.  

Mutations in DNAI1 and DNAH5 have been detected in 38% of patients with primary ciliary dyskinesia. Commercial testing is available for all mutations in these 2 genes.  A diagnostic yield of 69% has been reported by combining ciliary biopsy and molecular genetics. [10]

Ciliary Biopsy

In North America ciliary biopsy for electron microscopy to detect ciliary ultrastructural abnormalities is used in conjunction with genetic testing while a combination of genetic testing and high speed videomicroscopy is used in Europe. [23] Electron microscopy will detect approximately 70% of PCD cases. [22]

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Imaging Studies

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  • Chest roentgenography may reveal changes due to chronic bronchitis and pneumonia. Dextrocardia, if present, is observed on chest roentgenographs. Bronchiectasis may be observed with recurrent lower respiratory infections.

  • Direct video cinematography or oscillography is used to analyze ciliary beat frequency and waveform.

  • Digital high-speed video (DHSV) imaging allows evaluation of ciliary beat pattern in 3 different planes in slow motion or frame-by-frame. Using DHSV imaging, patients with PCD can be classified into 3 distinct groups on the basis of ciliary beat pattern (see Pathophysiology).

  • Ciliary beat pattern analysis is a more sensitive and specific test for PCD with positive predictive value. [24]

  • Santamaria et al have studied structural lung disease in patients with PCD using a modified Brody composite high-resolution CT (HRCT) scoring system to evaluate the severity and distribution of lung abnormalities; they found that bronchiectasis, peribronchial thickening, and peripheral mucous plugging were the most common changes, followed by central mucus plugging and parenchymal abnormalities. [25]

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Other Tests

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  • Mucociliary clearance studies measure the perception of sweetness after saccharin is placed on the anterior portion of the inferior turbinate. A delayed or absent response suggests impaired mucociliary clearance. However, this test is not recommended 

  • Nasal nitric oxide measurements have been tried to screen children older than 5 years. [26, 27] Extremely low levels of nitric oxide (less than 100 nL/min) may be suggestive. [28] A portable nitric oxide analyzer has been validated for screening of PCD. [22] Very low levels of nasal nitric oxide may be found during acute viral respiratory infections and in some patients with cystic fibrosis.

  • Pulmonary function testing has shown reduced values for FEV1. [7, 29] Longitudinal studies have shown a high degree of variation in the course of lung function after diagnosis that was not related to either age or lung function level at the time of diagnosis. [29]

  • A prospective study of 654 consecutive patients showed that high-speed video miscopy analysis had an excellent sensitivity and specificity (100% and 93% respectively). The transmission electromicroscopy in combination with high-speed videomicroscopy was 100% sensitive and 92% specific. [23]  

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Procedures

Bronchoscopy reveals mucosal inflammation and mucopurulent secretions. It can also be used to confirm the reversal of bronchial anatomy in those patients with situs inversus.

Examination of the ciliary ultrastructure by electron microscopy in a nasal or bronchial ciliary biopsy sample can be used as a diagnostic test.

Nasal biopsy (brush or curettage) samples are obtained from inferior surface of turbinates. Electron microscopy reveals the abnormalities in the cilia.

Bronchial brush biopsy demonstrates ciliary ultrastructure abnormalities using an electron microscope. Due to the varying orientation of the cilia in a biopsy specimen and resultant technical difficulties in the full analysis of cilia, a quantitative method includes assessing axonemal defects in less than perfectly oriented cilia, with dynein arms being assessed only in those cilia in which these small structures can be discerned.

A review of quantitative transmission electron microscopy in 1182 patients referred for ciliary structure analysis reported confirmation of diagnosis of PCD in 242 (20%) cases. [30] In addition to describing an algorithm including screening tests such as exhaled nasal nitric oxide, saccharine test, light microscopy, and electron microscopy, the authors describe the use of transmission electron microscopy using a rapid quantitative method. However, electron microscopy does not always exclude the diagnosis of PCD.

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