Diagnóstico de la discinecia ciliar primaria / Diagnosis of the primary ciliary dyskinesia

Primary ciliary dyskinesia is a congenital disorder due to abnormal motile ciliary function, especially in the airway epithelium. The mucociliary clearance is impaired, producing reoccurring respiratory tract infections, usually resulting in bronchiectasis as an adult. Patients also have frequent ear and sinus infections and almost 50% of them have situs inversus. Diagnosis of primary ciliary dyskinesia is difficult because there is not a single gold standard test, resulting in the need of a multi-test approach. Until recently in our country we only had transmission electron microscopy, but nasal nitric oxide and high speed video microscopy are now available. In this article we will detail the most important clinical characteristics that make us suspect the presence of primary ciliary dyskinesia at different ages and the methods available for its diagnosis.

La discinesia ciliar primaria es una enfermedad congénita debida a una alteración del movimiento normal de los cilios, especialmente a nivel del epitelio respiratorio. Esto se traduce en una alteración del clearance mucociliar lo que predispone al paciente a tener infecciones respiratorias repetidas, terminando en la aparición de bronquiectasias en la edad adulta. También son frecuentes las infecciones repetidas de oídos y cavidades perinasales. La presencia de situs inverso puede verse en hasta en 50% de los pacientes con esta enfermedad. El diagnóstico de discinesia ciliar primaria es difícil ya que no existe un examen que sea considerado patrón de oro, por lo que se requiere la realización de distintos exámenes. En nuestro país hasta hace poco tiempo solo contábamos con la microscopía electrónica, pero recientemente se ha sumado la medición de óxido nítrico nasal y la videomicroscopía de alta velocidad. En el presente artículo se detallarán las características clínicas más importantes que hacen sospechar la presencia de DCP en las distintas edades y los métodos disponibles para su diagnóstico.

Diagnosis of primary ciliary dyskinesia / Diagnóstico de discinesia ciliar primária

Primary ciliary dyskinesia (PCD) is a genetic disorder of ciliary structure or function. It results in mucus accumulation and bacterial colonization of the respiratory tract which leads to chronic upper and lower airway infections, organ laterality defects, and fertility problems. We review the respiratory signs and symptoms of PCD, as well as the screening tests for and diagnostic investigation of the disease, together with details related to ciliary function, ciliary ultrastructure, and genetic studies. In addition, we describe the difficulties in diagnosing PCD by means of transmission electron microscopy, as well as describing patient follow-up procedures.

Discinesia ciliar primária (DCP) é uma doença genética que compromete a estrutura e/ou a função ciliar, causando retenção de muco e bactérias no trato respiratório e levando a infecções crônicas nas vias aéreas superiores e inferiores, defeitos de lateralidade visceral e problemas de fertilidade. Revisamos os sinais e sintomas respiratórios da DCP, os testes de triagem e a investigação diagnóstica, bem como detalhes relacionados ao estudo da função, ultraestrutura e genética ciliar. Descrevemos também as dificuldades em diagnosticar a DCP por meio de microscopia eletrônica de transmissão, bem como o seguimento dos pacientes.

Disquinesia ciliar: diagnóstico ultraestructural, evolución clínica y alternativas de tratamiento / Clinical and ultrastructural features of ciliary dyskinesia

Background: Ciliary dyskinesia (CD) is a low incidence genetic illness, that presents with a wide clinical spectrum. Also, there are transitory conditions that present with ciliary anomalies, secondary to infectious diseases of the airways. Aim: To descube clinical and ultrastructural findings and clinical and therapeutic evolution of these patients. Patients and Methods: Retrospective review of medical records and electron microscopy findings of 33 patients (aged 1 to 21 years, 14 females) with ultrastructural diagnosis of CD. To obtain follow up information, a telephone survey was done. Results: In 30 patients (90 percent) the inner dynein arm (IDA) was absent in 50 or more percent of the cilia. Twenty two (66 percent) had absence of the outer dynein arm. Before diagnosis of CD, 19 patients (57 percent) presented recurrent otitis media, 25 patients (77 percent), three or more episodes of rhinosinusitis and 18 patients (56 percent) had recurrent pneumonia. Middle ear ventilation tubes were placed in 19 patients (57 percent), and during its use, 12 (68 percent) remained without othorrea. Sixteen patients (48 percent) with recurrent episodes of rhinosinusitis required adenoidectomy Seven (21 percent) required a functional endoscopic sinus surgery (FESS), and 6 (86 percent) improved after FESS. Conclusions: Our patients with CD presented recurrent infections in different airway locations. In those with a diagnosis of CD and recurrent otol¢gica! and rhinosinusal infections, IDA was absent in a high percentage of cilia. FESS and the use of ventilation tubes may have a beneficial role in a subgroup of patients with CD.

Chemotaxis of Blood Neutrophils from Patients with Primary Ciliary Dyskinesia

Primary ciliary dyskinesia is characterized by chronic upper and lower respiratory infections which are caused by the grossly impaired ciliary transport. Since the cilia and neutrophils both utilize microtubular system for their movement, it has been speculated that neutrophil motility such as chemotaxis might be impaired in patients with primary ciliary dyskinesia. Neutrophils were purified from whole blood from 16 patients with primary ciliary dyskinesia and from 15 healthy controls. Chemotactic responses of neutrophils to leukotriene B4 (LTB4), complement 5a (C5a), and formylmethion-ylleucylphenylalanine (fMLP) were examined using the under agarose method. The chemotactic differentials in response to LTB4, C5a, and fMLP in neutrophils from the patient group were significantly lower than the corresponding values in neutrophils from the control group (p<0.05 for all comparisons). The difference in chemotactic index between the two groups was statistically significant for LTB4 and fMLP (p<0.05 for both comparisons), but not for C5a (p=0.20). Neutrophils from patients with primary ciliary dyskinesia showed a decreased chemotactic response as compared with those from normal subjects. It is concluded that the increased frequency of respiratory tract infection in patients with primary ciliary dyskinesia is possibly due to the defective directional migration of neutrophils, as well as to the defective mucociliary clearance of the airways.

Discinesia ciliar primária / Primary ciliary diskinesia

Discinesia ciliar primária (DCP) é uma doença genética autossômica recessiva, caracterizada por defeito da motilidade de estruturas ciliadas. A propulsäo do espermatozóide e o clearance do muco estäo prejudicados. As manifestaçöes clínicas de interesse para o otorrinolaringologista säo: sinisite, otomastoidite, problemas na fala e olfato. O diagnóstico é feito por uma cascata de investigaçöes, iniciando com o teste de sacarina, frequência do batimento ciliar e microscopia eletrônica para verificar a morfologia e a orientaçäo ciliar. É importante que o diagnóstico seja precoce para previnir o desenvolvimento de bronquiectasia e para evitar qualquer procedimento otorrinolaringológico desnecessário. O tratamento da DCP é essencialmente sintomático. Os pilares säo a antibioticoterapia e a fisioterapia torácica. O seguimento contínuo é essencial, e o acompanhamento deve ser multidisciplinar, com o apoio de centros com interesse em DCP. O prognóstico é bom, mas a morbidade é considerável se a DCP for manuseada incorretamente.

Ultrastructure and chaetotaxy of sensory receptors in the cercaria of a species of Allopodocotyle Pritchard, 1966 (Digenea: Opecoelidae)

Previous investigations of sensory systems in opecoelid cercariae have focused on chaetotaxy and ultrastructure of sensory receptors. They revealed chaetotaxic patterns within family, genus, and species as well as different receptors. Chaetotaxic and ultrastructural observations have rarely been combined. We investigated the ultrastructure of cercarial sensory receptors in conjunction with chaetotaxy and neuromorphology in a species of Allopodocotyle. Cercariae were treated with acetylthiocholine iodide and silver nitrate, and some were processed for light, scanning (SEM), and transmission (TEM) electron microscopy. Five nerve regions were distinguished. Chaetotaxy was consistent with that of other opecoelids. Five types of receptors were distinguished with SEM. Types differed in number of cilium-like structures (one or more), length of cilium-like structure (short, moderately long, or long), presence or absence of a tegumentary collar, and length of tegumentary collar (low, moderately low, or very high). Internal ultrastructure of some types revealed unsheathed cilium-like structures, basal body, and thickened nerve collars. Possible subtegumentary and sheathed receptors are introduced. Some receptor types were site-specific. For example, receptors with multiple cilium-like structures were concentrated on cephalic region whereas receptors with short cilium-like structure were widespread throughout most regions. Ultrastructure and site-specificity observations suggest that most receptors are mechanoreceptors

Ultrastructural defects of the ciliary epithelium in a child with Kartagener's syndrome.

Kartagener's syndrome is a well known classical triad of presentations consisting of bronchiectasis, sinusitis and situs inversus. It is now recognized that the syndrome is an extreme presentation of primary ciliary dyskinesia, a large group of conditions with ultrastructural ciliary defects, leading to poor ciliary motility in various organ systems. A case of Kartagener's syndrome is presented in an eight year old Thai boy in whom the ultrastructural ciliary defects have been examined and described in detail for the first time in Thailand. Incomplete lack of dynein arms was recognized. In addition, disorientation of ciliary axis was noticed. Due to severe bronchiectatic changes of the right lower lobe and right lingular lobe which did not improve despite adequate antibiotics, these lobes were surgically removed. The child has done well since, but still suffers occasional and recurrent bouts of sinusitis.

Ultra-estrutura ciliar à microscopia eletrônica de transmissäo / Ciliary ultrastructure at transmission electron microscopy

A síndrome da discinesia ciliar é uma das hipóteses diagnósticas que devem ser consideradas em indivíduos com sintomatologia crônica pulmonar e de vias aéreas superiores. Nesta doença, os cilios do epitélio respiratório säo imóveis ou entäo apresentam um batimento descoordenado. Qualquer uma dessas situaçöes acaba por prejudicar o transporte mucociliar, um dos mais importantes mecanismos de defesa do aparelho respiratório. Acredita-se que anomalias estruturais ciliares possam levar a funcionamento inadequado dos cílios. Este trabalho teve como principais objetivos a identificaçäo dos elementos da ultra-estrutura ciliar normal à microscopia eletrônica de transmissäo e também a análise desta ultraestrutura em pacientes com diagnóstico clínico de síndrome de discinesia ciliar. Participaram do estudo oito pacientes e quatro controles normais. Quatro dos pacientes eram também portadores da síndrome de Kartagener. A comparaçäo dos resultados obtidos em controles e casos permitiu o diagnóstico de anomalias ultra-estruturais em quatro pacientes. Os defeitos identificados foram: deficiência de braços externos de dineína em dois pacientes, e deficiência de braços internos de dineína e alteraçäo de filamentos radiais em outros dois pacientes. Três pacientes com diagnóstico clínico de discinesia ciliar dmonstraram ter ultra-estrutura ciliar normal. Deste grupo, fazia parte um indivíduo com síndrome de Kartagener. O oitavo paciente apresentou também ultra-estrutura ciliar normal, fato que somado à presença de azoospermia obstrutiva leva ao diagnóstico de síndrome de Young. Alguns achados ultra-estruturais deste trabalho discordam das informaçöes da literatura sobre o assunto. Este é o caso, por exemplo, do pé basal, estrutura que a maioria dos autores apresenta como única; no entanto, foi bastante freqüente neste material a observaçäo de pés basais duplos e até triplos, tanto em controles como em casos

Ultrastructural abnormalities of cilia secondary to chronic pulmonary infections: a prospective study

The cilia are an essential component of the respiratory defense system. Certain ciliary abnormalities are produced by chronic infections. In this prospective study, ultra-structural features of cilia are described in 46 subjects. Thirty patients were studied for the problem of recurrent chest infections; of these, 6 showed ciliary abnormalities which were specific and diagnostic of primary ciliary dyskinesia. In 24 patients there were other abnormalities which were presumably secondary to chronic infections. This paper describes the various ciliary abnormalities seen in the latter group. It is emphasized that, as ciliary abnormalities may be the result rather than the cause of infections, a diagnosis of primary ciliary dyskinesia should be made with caution

Atypical cilia in the choroid plexus of guineapig.

Ultrastructural study of choroid plexus of normal and kaolin induced hydrocephalic guineapigs showed clusters of cilia arising from the apical part of some of the epithelial cells. Some of these cells had typical 9 + 2 cilia, while most of the control and the hydrocephalic groups showed 9 + 0 type of cilia. These atypical (9 + 0 type) cilia of choroidal epithelium differ from the primary cilia of other mammalian tissues in that, clusters of long cilia arise from a single cell and have no associated centrioles within the cytoplasm. They may be motile and sensory (osmoregulator or pressure sensor or both) in nature.

Ultraestrutura ciliar a microscopia electrônica de transmissäo: comparaçäo da prevalência de anomalias ciliares entre pacientes portadores da sindrome da discinesia ciliar e individuos normais; 2v / Ciliary ultraestructure at electronic microscopy of transmission: comparison of the prevalence of ciliary anomaly between patients with ciliary diskenesia syndrome and normal individuals

Este trabalho teve como objetivo a identificaçäo dos elementos ultraestrutura ciliar normal a microscopia eletrônica de transmissäo e também a análise em pacientes com diagnóstico clínico da síndrome da discinesia ciliar. Participaram 8 pacientes sendo que o resultado diagnosticou 4 com anomalias ultraestrutural, 2 com deficiência de braços externos de dineina, e outros 2 com deficiência de braços internos de dineina e alteraçäo de filamentos radiais. Alguns achados ultraestruturais deste trabalho discordam das informaçöes da literatura sobre o assunto