Primary ciliary dyskinesia: Diagnosis in children with inconclusive ultrastructural evaluation

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.

Nasal nitric oxide and nitric oxide synthase expression in primary ciliary dyskinesia

“…In all subjects, ciliary motion analysis, ultrastructural assessment of cilia on nasal brushings and nNO measurement were performed. nNO measurements, nasal brush biopsy, ciliary motion analysis and ultrastructural studies were performed according to standard methodologies [12][13][14][15][16], detailed in the online supplementary material.…”

Different Levels of Exhaled Nasal Nitric Oxide in Patients Diagnosed with Primary Dyskinesia

“…The diagnosis of PCD is based on the confirmation of typical Ultra structural defects by transmission electron microscopy and abnormal ciliary motion analysis and is identified in ~90% of patients; it also involves the outer dynein arms, inner dynein arms, or both [2,3]. The majority of these patients have an early onset of symptoms [1,2], and neonatal respiratory distress is common [11,12]; but there are patients with PCD that have minimal or absence of transmission electron microscopy found defects (i.e., atypical PCD or SCD), and a wide spectrum of disease variability [1,[19][20][21][22]. The impaired mucociliary clearance is commonly associated with recurrent or chronic respiratory tract infections leading to sinusitis, serous otitis media, rhinitis, bronchitis and pneumonia.…”

Complete Ciliary Aplasia; a Rare Form of Primary Ciliary Dyskinesia

“…Transmission electron microscopy is an essential part of diagnostic testing, but the benefit of ultrastructural findings as criteria for the diagnosis of PCD is sometimes limited [11]. Normal ciliary ultrastructure has been reported in few patients with immotile cilia.…”