Cross-sectional evaluation of the saccharin transit time test for primary ciliary dyskinesia: did we discard this tool too soon?

BACKGROUND: Primary ciliary dyskinesia (PCD) is a rare and heterogeneous disease that is difficult to diagnose and requires complex and expensive diagnostic tools. The saccharin transit time test is a simple and inexpensive tool that may assist in screening patients with PCD. OBJECTIVES: This study aimed to compare changes in the electron microscopy findings with clinical variables and saccharin tests in individuals diagnosed with clinical PCD (cPCD) and a control group. DESIGN AND SETTING: An observational cross-sectional study was conducted in an otorhinolaryngology outpatient clinic from August 2012 to April 2021. METHOD: Patients with cPCD underwent clinical screening questionnaires, nasal endoscopy, the saccharin transit time test, and nasal biopsy for transmission electron microscopy. RESULTS: Thirty-four patients with cPCD were evaluated. The most prevalent clinical comorbidities in the cPCD group were recurrent pneumonia, bronchiectasis, and chronic rhinosinusitis. Electron microscopy confirmed the clinical diagnosis of PCD in 16 of the 34 (47.1%) patients. CONCLUSION: The saccharin test could assist in screening patients with PCD due to its association with clinical alterations related to PCD.

Challenges in Diagnosing Primary Ciliary Dyskinesia in a Brazilian Tertiary Hospital.

Primary ciliary dyskinesia (PCD) causes cellular cilia motility alterations, leading to clinical manifestations in the upper and lower respiratory tract and situs abnormalities. The PCD diagnosis was improved after the inclusion of diagnostic tools, such as transmission electron microscopy and genetic screening; however, the PCD screening is a challenge yet. In this context, we aimed to describe the clinical, genetic, and ultra-ciliary characteristics in individuals with clinical suspicion of PCD (cPCD) from a Brazilian Tertiary Hospital. An observational study was carried out with individuals during the follow-up between 2011 and 2021. The individuals were submitted to clinical questionnaires, transmission electron microscopy, and genetic screening for pathogenic variants in PCD-related genes. Those patients were classified according to the degree of suspicion for PCD. In our study, we enrolled thirty-seven cPCD individuals; 20/37 (54.1%) had chronic rhinosinusitis, 28/37 (75.6%) had bronchiectasis, and 29/37 (78.4%) had recurrent pneumonia. A total of 17/37 (45.9%) individuals had transmission electron microscopy or genetic confirmation of PCD; 10 individuals had at least one positive pathogenic genetic variant in the PCD-related genes; however, only seven patients presented a conclusive result according to the American College of Medical Genetics and Genomics and the Association for Molecular Pathology with two pathogenic variants in homozygous or compound heterozygous. The median age at diagnosis was 13 years, and the median time between suspicion and diagnosis was four years. Sixteen patients had class I electron microscopy alterations, seven had class II alterations, and 14 had normal transmission electron microscopy according to the international consensus guideline for reporting transmission electron microscopy results in the diagnosis of PCD (BEAT-PCD TEM Criteria). Genetic screening for pathogenic variants in PCD-related genes and transmission electron microscopy can help determine the PCD diagnosis; however, they are still unavailable to all individuals with clinical suspicion in Brazil. We described ultrastructural alterations found in our population along with the identification of pathogenic variants in PCD-related genes.

Histologic and Ultrastructural Findings in Dogs With Chronic Respiratory Disease Suspected of Ciliary Dyskinesia.

Mucociliary clearance is a main defense mechanism of the respiratory tract, which can be inherently impaired in primary ciliary dyskinesia (PCD) or reversibly altered in secondary ciliary dyskinesia (SCD). Limited diagnostic test availability likely leads to misdiagnosis or underdiagnosis of PCD in animals. This study evaluated the light and transmission electron microscopy (TEM) changes in the respiratory mucosa of 15 dogs with chronic respiratory disease suspected of PCD. Necropsy was performed in 1 case and 2 dogs were used as negative controls. PCD was confirmed in 1 dog, which presented with chronic otitis, bronchopneumonia, hydrocephalus and ultrastructural abnormalities in 84% of the assessed cilia, including absence of dynein arms and microtubular changes. The 14 other cases showed only nonspecific alterations, such as ciliary disorientation, compound cilia, ciliary edema, and axoneme bubbles in a minority of the evaluated cilia and were classified as SCD. Ciliary ultrastructural analysis can confirm a diagnosis of PCD if specific abnormalities exist. TEM remains an important investigational tool in veterinary medicine, as no other specific test for PCD in dogs has been standardized yet.

Ciliary ultrastructure in patients with chronic rhinosinusitis and primary ciliary dyskinesia.

The Cilia represent one of the main mechanisms contributing to the clearance of microorganisms and particles from the respiratory epithelium. Primary ciliary dyskinesia (PCD) is a genetically determined disorder characterized by irreversible systemic dysmotility of the cilia. Secondary ciliary dyskinesia (SCD) differs from primary defects on the reversible ultrastructural alterations that can occur after any insult to a previously normal mucosa. Hence, this study aimed to describe and compare the main ultrastructural ciliary features in PCD and SCD through transmission electron microscopy. The most frequent PCD abnormalities were missing or short dynein arms, missing central microtubules, and displacement of one of the nine peripheral doublets. The most common changes found in SCD were compound cilia and peripheral microtubule alterations associated with modifications of the respiratory epithelium. PCD presented a higher percentage of altered cilia (>30 %) when compared to SCD (5 %), demonstrating that SCD is more limited in area than PCD. Whereas in PCD the changes in the dynein arms and in the central microtubules are fundamental for diagnostic confirmation, the diagnosis of SCD usually involves compound cilia and disarrangements in peripheral microtubules.

Primary ciliary dyskinesia: evaluation using cilia beat frequency assessment via spectral analysis of digital microscopy images.

Ciliary beat frequency (CBF) measurements provide valuable information for diagnosing of primary ciliary dyskinesia (PCD). We developed a system for measuring CBF, used it in association with electron microscopy to diagnose PCD, and then analyzed characteristics of PCD patients. The CBF measurement system was based on power spectra measured through digital imaging. Twenty-four patients suspected of having PCD (age 1-19 yr) were selected from a group of 75 children and adolescents with pneumopathies of unknown causes. Ten healthy, nonsmoking volunteers (age ≥ 17 yr) served as a control group. Nasal brush samples were collected, and CBF and electron microscopy were performed. PCD was diagnosed in 12 patients: 5 had radial spoke defects, 3 showed absent central microtubule pairs with transposition, 2 had outer dynein arm defects, 1 had a shortened outer dynein arm, and 1 had a normal ultrastructure. Previous studies have reported that the most common cilia defects are in the dynein arm. As expected, the mean CBF was higher in the control group (P < 0.001) and patients with normal ultrastructure (P < 0.002), than in those diagnosed with cilia ultrastructural defects (i.e., PCD patients). An obstructive ventilatory pattern was observed in 70% of the PCD patients who underwent pulmonary function tests. All PCD patients presented bronchial wall thickening on chest computed tomography scans. The protocol and diagnostic techniques employed allowed us to diagnose PCD in 16% of patients in this study.

Avaliação da ultraestrutura e do movimento ciliar em crianças com pneumopatias crônicas e de repetição se diagnóstico definido / Evaluation of the ultrastructure and of the movement of cilia in children with chronic and repetition pneumopathies without a defined diagnosis

INTRODUÇÃO: A discinesia ciliar primária é uma doença genética que se caracteriza pela alteração da ultraestrutura e função do cílio móvel, com consequentes alterações do transporte mucociliar, causando infecções das vias aéreas superiores, inferiores e infertilidade. O diagnóstico, realizado por avaliação da ultraestrutura ou pesquisa de mutação genética, é feito mediante critérios de seleção de pacientes e testes de screening. Esta pesquisa avalia a ultraestrutura e frequência de batimento ciliar, propõe um modelo de investigação de discinesia ciliar primária, e caracteriza os pacientes diagnosticados. MÉTODO: Foi realizado um estudo transversal controlado entre janeiro de 2007 e julho de 2009, no Ambulatório de Pneumologia Pediátrica do Instituto da Criança. Foram selecionadas 28 crianças e adolescentes (6 meses a 19 anos, de ambos os sexos), de uma população de 75 crianças com pneumopatias crônicas e de repetição sem diagnóstico definido, que apresentavam ao menos um dos seguintes achados: bronquiectasia de causa desconhecida, doença de vias aéreas superiores com sintomatologia crônica, infecções pulmonares de repetição, dextrocardia e/ou situs inversus acompanhados de sintomas em vias aéreas superiores e/ou inferiores, e asma de difícil controle com sintomas em vias aéreas superiores e/ou inferiores. A presença de pneumopatias crônicas com diagnóstico definido foi utilizada como critério de exclusão por meio dos seguintes exames: dois testes do suor (exclusão de fibrose cística), tomografia computadorizada do tórax (suspeita de bronquiolite obliterante), dosagem de alfa-1 antitripsina (investigação de déficit de alfa-1 antitripsina), e exames de investigação das imunodeficiências mais frequentes (hemograma, dosagens de imunoglobulinas, contagem de linfócitos T e B, sorologias para avaliação da produção ativa de anticorpos, PPD e HIV). Foi desenvolvido um sistema medição da frequência de batimento ciliar, baseado em análise espectral. Dez adultos...

INTRODUCTION: Primary ciliary dyskinesia (PCD) is a genetic disorder of the ultrastructure and function of mobile cilia, with consequent impairment of mucociliary clearance, leading to upper and lower airways respiratory infection and infertility. The diagnosis, based on ultrastructure evaluation or genetic scan, is performed according to patient selection and screening tests. This research evaluates cilia ultrastructure and beat frequency, proposes a model for investigating primary ciliary dyskinesia, and characterizes the patients diagnosed.METHOD: A controlled and observational study was carried out at the Pediatric Pulmonology Ambulatory of the Instituto da Criança between January 2007 and July 2009. Twenty eight children and teenagers (ages between 6 months and 19 years) were selected, from a population of 75 patients with chronic and repetition pneumopathies without a defined diagnosis, which met at least one of the following inclusion criteria: bronchiectasis of unknown cause, upper respiratory disease with chronic symptoms, repetition pulmonary infections, dextrocardia and/or situs inversus with symptoms in upper and/or lower respiratory airways, and asthma of difficult control with symptoms in upper and/or lower respiratory airways. The presence of cronic pneumopathies with a defined diagnosis was used as exclusion criterion, based on the following exams: two sweat tests (cystic fibrosis exclusion), lung CT scan (bronchiolitis obliterans exclusion), seric levels of alpha-1 anti-trypsin (alpha-1 anti-trypsin deficit evaluation), and evaluation of more frequent immunodeficiency disorders (white blood cells, T and B lymphocytes levels, and sorology tests for humoral immunity, PPD and HIV). A cilia beat frequency measurement system was developed, based on spectral analysis. Ten healthy adult volunteers (ages greater than or equal to 17 years old, of both sexes), without an acute respiratory...

Caso clínico: síndrome de Kartagener / Kartagener syndrome: case report / La síndrome de Kartagener: relato de caso

Objetivo: descrever um caso da síndrome de Kartagener e alertar os pediatras para o diagnóstico da discinesia ciliar primária. Relato do caso:paciente de 17 anos, sexo feminino, que apresentava desde o primeiro ano de vida, tosse, secreção nasal, otorréia, sibilância e 15 episódios de pneumonia. Os exames de imagem mostraramsinusopatia maxilar bilateral, situs inversus totalis, bronquiectasias nas bases pulmonares, áreas de condensação e bronquiolectasias difusas com aspecto de “árvore em brotamento”. A espirometria mostrou distúrbio obstrutivo leve, sem resposta a broncodilatador. As duas dosagensde cloro no suor e as imunoglobulinas séricas foram normais. O teste de triagem para avaliação do transporte mucociliar (teste da sacarina)teve resultado alterado (40 min), caracterizando a discinesia ciliar. Com base nesse resultado, a presença de situs inversus, bronquiectasias e sinusopatia crônica, foi estabelecido o diagnóstico da síndrome de Kartagener. Conclusão: a suspeita de discinesia ciliar é facilitada quando ocorre o situs inversus, o que caracteriza a síndrome de Kartagener. Porém, deve-se atentar para o fato de que a maioria dos casos de discinesia ciliar não têm essa má formação associada.

Objective: to describe a case of Kartagener syndrome and alert pediatricians for the diagnosis of primary ciliary dyskinesia. Case report:a 17 year-old patient, female, presented since her first year of life cough, nasal secretion, otorrhea, sibilance and 15 episodes of pneumonia. Image exams have shown bilateral maxillary sinusopathy, situs inversus totalis, bronchiectasis at pulmonary bases, condensation areas and diffuse bronchiolectasis with “sprouting tree”aspect. The spirometry shown a light obstructive disorder without response to bronchodilator. Two chlorine exams in the sweat and the seric immunoglobulin were normal. The test to evaluatethe mucociliary transport (saccharin test) had altered result (40 minutes), characterizing the ciliary dyskinesia. Based on this result, and the presence of situs inversus, bronchiectasis and chronic sinusopathy, the diagnosis of Kartagener syndrome was established. Conclusion: the suspicion of ciliary dyskinesia is easier when a situs inversus, is found, which characterizes the Kartagener syndrome. However, it shall be no ticed that most of the ciliary dyskinesia cases does not present this malformation associated.

Objetivo: discrebir un caso síndrome de Kartagener y alertar los pediatras para el diagnostico de discinesia ciliar primaria. Relato del caso: una paciente de 17 años, presentaba desde el primeraño de vida toss, secreción nasal, otorrea, sibilancia em el pecho, con histórico de 15 episodios de neumonia. Los exames auxiliares de imagen mostaran sinusitis maxilar bilateral, situs inversus totalis, bronquiectasias nas bases pulmonares,áreas de condensación y ronquiectasias difusas, com aspecto de arbol en brote. La espirometria mostro distúrbio obstrutivo pequeño sin respuestaa lo broncodilatador. Los niveles de cloro en el suor y de las inmunoglobulinas sericas fuerannormales. Lo testigo de triage para evaluar el transporte mucociliar con sacarina tubo resultado alterado (40 minutos), caracterizando el diagnosticode síndrome de Kartagener. Conclusión: la sospecha de discinesia ciliar es facilitada cuando hay el situs inversus, que es caracteristico de la síndrome de Kartagener. Pero, es necessário atentara que circa de la mitad de los casos de discinesia ciliar non tiene esta ma-formación.

Radiofrequency catheter ablation of an accessory pathway in a patient with Wolff-Parkinson-White and Kartagener's syndrome.

We report a case of a manifest left free wall accessory pathway in a patient with Kartagener's syndrome and recurrent episodes of orthodromic atrioventricular reentrant tachycardia. To the best of our knowledge, it is the first report of Wolff-Parkinson-White syndrome associated with Kartagener's syndrome. Situs inversus and mirror image dextrocardia occurred with no additional detectable cardiac structural abnormalities. Diagnostic and therapeutic electrophysiological study was carried out via transaortic approach and a left-to-right reversal of monoplane fluoroscopic image.

Síndrome de kartagener: comunicación de un caso y revisión de algunos aspectos / Kartageners Syndrome: comunication of a Case and review of some aspectos

Se comentan las características clínicas del síndrome de Kartagener. Se analizan sus diferentes corrientes etiopatogénicas presentando un caso clínico que lo ilustra. Se comentan los métodos diagnósticos más importantes y se insiste en el trabajo quirúrgico como terapéutica fundamental en este síndrome(AU)

Síndrome de Kartagener / Kartagener's syndrome

A síndrome de Kartagener consiste em uma tríade de sintomas, determinada geneticamente, afetando a atividade de proteínas importantes ao movimento ciliar, sobretudo no trato respiratório e espermatozóides. Trata-se de uma patologia pouco comum, responsável pelo aumento na sucetibilidade dos pacientes às infecçoes respiratórias. Os autores apresentam um relato de caso, em paciente pediátrico, e fazem uma breve revisao bibliográfica, dando ênfase aos aspectos anatomopatológicos da doença.

[Kartagener's syndrome. A case report]. / Síndrome de Kartagener. Presentación de un caso.

A case of Kartagener's syndrome (situs inversus, sinusitis and bronchiectasis) is reported at the "Comandante Manuel Fajardo" Teaching Clinico-surgical Hospital, Havana City, in a patient aged 33 years, who presents the three elements of Kartagener's triad. The case was investigated in the Department of Medicine and Department of Radiology. The literature on this uncommon syndrome was reviewed and it was found that there are an open prevalence of this entity in children younger than 15 years, as well as severe respiratory complications in affected patients. Emphasis is made on the importance of early diagnosis and adequate treatment of affections of high respiratory passages, which allows an orientation to avoid future bronchiectasis and sinusopathies. Genetic aspects, as well as incidence of suffering variants, are mentioned. Emphasis is made on specific nursing procedures of this syndrome.