PCD Biopsy

Motile cilia line the respiratory tract and beat in a synchronous fashion to clear mucus, dust and bacteria thus protecting the body from infection.  Primary Ciliary Dyskinesia (PCD) is a rare genetic disease (1:7,500 in the UK) in which ciliary movement is compromised and mucus is not cleared effectively. PCD is characterised by chronic runny nose and wet cough, recurrent chest infections and in the worst cases bronchiectasis (irreversible lung damage).

PCD is diagnosed using a combination of tests as although Transmission Electron Microscopy (TEM) was regarded as the gold standard for PCD diagnosis, it is now clear that using TEM alone misses about 15% of positive PCD cases. TEM is ideally performed in combination with clinical tests such as nasal nitric oxide measurement and laboratory tests including high speed video microscopy, immunofluorescence and in special cases electron tomography. Genetic testing is playing an increasingly important role in PCD diagnosis.

Examination of ciliary ultrastructure can identify changes in cilia such as missing components of the cilia or disarrangement of the microtubules, both of which are indicative of PCD.

For TEM, sample of epithelium, taken from the nose or bronchus using a cytology brush, is fixed in glutaraldehyde, pelleted into a gel and processed for TEM as usual. Resin blocks containing cells are cut, stained and examined at high magnification. The sample is assessed qualitatively and quantitatively, counting defects in dynein arms and microtubular arrangement. Guidelines for the use of TEM and reporting of results in PCD diagnosis are set out in an international consensus document. https://erj.ersjournals.com/content/55/4/1900725.long

In 2006 a national diagnostic service was commissioned by the NHS to provide access to diagnosis throughout England. 3 specialised diagnostic centres, (University Hospitals of Leicester, the Royal Brompton Hospital in London and University Hospital Southampton) were established. Later, a management service was commissioned, and an extra centre (Leeds/Bradford) added. The Scottish service was established in 20??.

It is important to note that:

  • TEM alone cannot rule out at positive PCD diagnosis
  • Secondary ciliary defects are observed in cases of infection or inflammation, and in samples with have not been adequately prepared.
  • Expert interpretation is always required.

For more information contact:

Dr Patricia Goggin, PCD Scientist, Biomedical Imaging Unit, University Hospital Southampton (p.goggin@soton.ac.uk)

Royal Brompton Hospital: www.rbht.nhs.uk/our-services/primary-ciliary-dyskinesia

PCD Support UK: https://pcdsupport.org.uk


Electron micrographs showing normal ciliary ultrastructure in cross section at a) the core of the ciliary axoneme with a 9+2 microtubular arrangement; b) the tip of the cilium with single microtubules; and c) the base of the axoneme.
Figure from Amelia Shoemark et al. Eur Respir J 2020;55:1900725 ©2020 by European Respiratory Society



Electron micrographs and diagrams of Class 1 ultrastructural defects in cross section. a) Outer dynein arm (ODA) defect; b) ODA and IDA defect; c) microtubular disorganisation and IDA defect.
Figure from Amelia Shoemark et al. Eur Respir J 2020;55:1900725 ©2020 by European Respiratory Society