Analysis of lung’s microscopic cilia ‘escalator’ key to tackling rare condition
State-of-the-art analysis of moving cilia from our airways can help diagnose a rare lung condition, scientists say.
Researchers from Southampton and Dundee have published their advice in the European Respiratory Journal.
Observing the ‘mucociliary escalator’
Cilia are moving ‘hair-like’ structures that line the surface of several body tissues.
There are over 200 cilia per airway epithelial cell. Normal coordinated beating acts as a moving ‘mucociliary escalator’ to propel mucus with trapped pathogens and particulates out from the lungs. We can harvest upper airway cells from patients by gently rubbing a small sampling brush on the inside of the nose cavity.
High-speed video microscopy can be used to record fast cilia ‘beating’, so that slow replay of videos can be analysed. Experienced scientists use this footage to describe and measure how cilia move.
The analysis provides important insight into an inherited lung condition called primary ciliary dyskinesia (PCD). This rare disorder of cilia (a ciliopathy) causes a lack of lung mucus clearance leading to repeated infection and progressive lung damage. Several functional tests, including high-speed video microscopy, are needed for diagnosing PCD.
Functional cilia testing underpins genetic profiling of patients with different variants, particularly difficult to confirm genetic variants (of uncertain significance (VUS)).
European paper
The new ‘Methods for the assessment of human airway ciliary function’ paper is written by Southampton’s Dr Claire Jackson and Dr Mathieu Bottier from the University of Dundee.
Dr Jackson is a Senior Research Fellow and PCD scientist at the NIHR Southampton Biomedical Research Centre.
“Ciliary function analysis is key in helping diagnose PCD, enabling patients to start treatment as quickly as possible,” she says. “In our new paper, we advise on how state-of-the-art high-speed video microscopy needs standardisation to be properly applied. A key future development would be to standardise ‘language’ to describe different abnormal ciliary movements. We also need to find commercial tools for better automated quantitative analysis of cilia.
“This technique can be used to research the effects of drugs and infection on the integrity of healthy or diseased airway cilia in culture. Non-inherited (secondary) ciliary dysfunction is also be seen in other lung diseases (such as asthma, cystic fibrosis, unexplained bronchiectasis and chronic obstructive pulmonary disease) and so we invite collaboration.”
Southampton’s collaborative research
The PCD group, led by Prof Jane Lucas, collaborate with Prof Baralle and Prof Holloway on PCD genetic detection. Together they have just published in Frontiers in Cell and Developmental Biology demonstrating gene expression changes in human airway cultures over time, and how representative airway cultures are to samples taken straight from a person’s airway.
Airway culture modelling is important for the BRC research strategy. Dr Jackson was pleased to played a part in a recent large collaborative review on lung modelling in Southampton. The paper, led by NIHR Southampton BRC’s Prof Tom Wilkinson, has been published in the European Respiratory Journal.