Understanding Primary Ciliary Dyskinesia: Experience From a Mediterranean Diagnostic Reference Centre

Abstract

Background: Due to the lack of a gold standard diagnostic test, reference centres with experienced personnel and costly procedures are needed for primary ciliary dyskinesia (PCD) diagnostics. Diagnostic flowcharts always start with clinical symptoms. Therefore, the aim of this work is to define differential clinical criteria so that only patients clinically compatible with PCD are referred to reference centres. Materials and methods: 18 variables from 476 Mediterranean patients with clinically suspicious PCD were collected. After analysing cilia function and ultrastructure, 89 individuals were diagnosed with PCD and 387 had a negative diagnosis. Simple logistic regression analysis, considering PCD as a dependent variable and the others as independent variables, was done. In order to define the variables that best explain PCD, a step-wise logistic regression model was defined. Aiming to classify individuals as PCD or PCD-like patients, based on variables included in the study, a classification and regression tree (CART) was designed. Results and conclusions: Simple logistic regression analysis shows statistically significant association between age at the beginning of their symptomatology, periodicity, fertility, situs inversus, recurrent otitis, atelectasis, bronchiectasis, chronic productive cough, rhinorrea, rhinusinusitis and recurrent pneumonias, and PCD. The step-wise logistic regression model selected situs inversus, atelectasis, rhinorrea, chronic productive cough, bronchiectasis, recurrent pneumonias, and otitis as PCD predictive variables (82% sensitivity, 88% specificity, and 0.92 Area Under the Curve (AUC)). A decision tree was designed in order to classify new individuals based on pansinusitis, situs inversus, periodicity, rhinorrea, bronchiectasis, and chronic wet cough.

High-Speed Video Microscopy for Primary Ciliary Dyskinesia Diagnosis: A Study of Ciliary Motility Variations with Time and Temperature

“…(2) the success rate of ALI-cultured nasal epithelium varies from 54% to 79%. Since the diagnostic process is costly and time-consuming, and requires specialized and trained staff, it is performed in reference centers [8]. One of the main problems of this rare disease is that it is often diagnosed late, worsening prognostics, especially at the respiratory level [14].…”

“…At present, there is no “gold standard” technique for the diagnosis of PCD [ 2 ], and a combination of different tests is required: analysis of the ciliary beat pattern (CBP) and ciliary beat frequency (CBF) [ 3 ] by high-speed video microscopy (HSVM) [ 4 , 5 ], the study of ciliary ultrastructure by transmission electron microscopy (TEM) [ 6 ], and genetic diagnosis [ 7 ]. In addition, nasal nitric oxide (nNO) determination is sometimes used as a screening test [ 8 ], and immunofluorescent labeling of specific proteins of the ciliary structure is emerging as another potential test that still needs to be validated [ 9 ]. Although TEM and genetics are two definitive diagnostic tests, 20–30% of cases of PCD show [ 9 ] normal ciliary ultrastructure.…”

“…However, there are important disadvantages when comparing with direct observation of the samples of nasal ciliary cells: (1) ALI culture requires highly specialized personnel and expensive material; (2) the success rate of ALI-cultured nasal epithelium varies from 54% to 79%. Since the diagnostic process is costly and time-consuming, and requires specialized and trained staff, it is performed in reference centers [ 8 ]. One of the main problems of this rare disease is that it is often diagnosed late, worsening prognostics, especially at the respiratory level [ 14 ].…”

IFT46 Expression in the Nasal Mucosa of Primary Ciliary Dyskinesia Patients: Preliminary Study

“…PCD is characterised by a malfunction (or absence) of respiratory ciliary activity, preventing proper mucociliary clearance, and thus leading to chronic respiratory infection. 13 , 15 Three principal factors regulate mucociliary clearance: ciliary activity, the composition of mucus and periciliary fluid, and cilia length. 3 , 18 , 23 The ciliary activity has been investigated extensively in PCD patients, and two major populations of PCD patients may be distinguished on this basis; the patients showing ultrastructural defects and those that exhibit normal ciliary ultrastructure but slow (or ineffective) beat activity due to dysfunction of metabolic enzymes involved in ATP or GTP synthesis, mutations in dynein genes such as DNAH11 , or other unexplored factors.…”

“…Ciliary beat frequency (CBF) and pattern (CBP) were measured within 180 min after biopsy at room temperature by HSVM, as outlined previously. 15 To corroborate the results, each nasal biopsy was plated on tissue culture plates coated with human collagen (type IV, Vitrogen-100; Cohesion Technologies, Palo Alto, CA) and incubated in DMEM at 37 °C in a humidified atmosphere of 5% CO 2 in the air for 24 h. The CBF and the CBP were then measured a second time.…”