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Primary ciliary dyskinesia: diagnosis in children with inconclusive ultrastructural evaluation
M Pifferi1, A M Cangiotti, V Ragazzo
1Department of Pediatrics, University of Pisa, Pisa, Italy. m.pifferi@med.unipi.it
Insights
This study differentiates acquired from genetic ciliary defects in children with chronic respiratory issues. It identifies primary ciliary dyskinesia (PCD) even with subtle or absent ultrastructural abnormalities.
Area of Science:
- Pediatric Pulmonology
- Cell Biology
- Genetics
Background:
- Chronic respiratory diseases in children can stem from acquired or genetic ciliary abnormalities.
- Accurate diagnosis is crucial for appropriate treatment and management.
Purpose of the Study:
- To differentiate acquired ciliary defects from genetically determined ones in children with severe chronic respiratory diseases.
- To establish a diagnostic method for primary ciliary dyskinesia (PCD) when ultrastructural defects are minimal or absent.
Main Methods:
- Transmission electron microscopy (TEM) analyzed nasal ciliated epithelium from 50 pediatric subjects.
- Patients were grouped based on TEM findings: Group A (inflammation-related defects) and Group B (defects resembling PCD).
- Phase contrast microscopy (PCM) assessed ciliary beat frequency and waveform before and after a 6-month treatment protocol.
Main Results:
- Group A showed inflammation-associated ciliary alterations; Group B had more central pair and dynein arm defects, similar to PCD.
- Children with low ciliary beat frequency (< 7 Hz) received physiotherapy and antibiotics.
- Post-treatment, nearly 50% of Group B and two in Group A maintained low ciliary beat frequency, indicating PCD.
Conclusions:
- A diagnostic approach combining TEM and PCM can identify PCD even with subtle or absent specific ultrastructural defects.
- This method aids in diagnosing primary ciliary dyskinesia in children where traditional markers are not definitive.
- Early and accurate diagnosis of PCD is vital for managing chronic respiratory conditions in children.
Abstract:
The purpose of this study was to distinguish between acquired and genetically determined ciliary abnormalities in children with severe chronic respiratory diseases. Samples of nasal ciliated epithelium from 50 subjects (25 male, 25 female; age-range 2-19 years) with severe chronic respiratory diseases were examined using transmission electron microscopy (TEM). Based on TEM findings, patients were divided into two groups: A and B. Group A comprised 39 children with ciliary alterations compatible with a condition probably occurring secondary to chronic inflammation (alterations of peripheral pairs, swollen cilia, and compound cilia). The other 11 patients, Group B, exhibited a greater number of alterations of the central pair and dynein arms (p< 0.001), which were qualitatively similar to, but less numerous than, those observed in primary ciliary dyskinesia (PCD). In both groups, analysis of ciliary beat frequency and waveform was performed by phase contrast microscopy (PCM). All the children with a ciliary beat frequency of < 7 Hz were treated with daily physiotherapy and with antibiotics, as recommended for PCD, for a 6-month period. After this treatment, the children were reexamined by PCM. Almost 50% of the children from Group B (i.e. those with a small proportion of specific ultrastructural defects) showed permanence of low ciliary beat frequency. This was also observed in two children of Group A. These children were considered to be affected by PCD. Our study describes a method for the diagnosis of PCD in the absence of specific ultrastructural defects or when these defects are present in only a small proportion of the cilia.