RESUMO
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.
Assuntos
Síndrome de Kartagener , Pneumonia , Humanos , Síndrome de Kartagener/diagnóstico , Síndrome de Kartagener/patologia , Estudos Transversais , Sacarina , Microscopia Eletrônica de TransmissãoRESUMO
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.
Assuntos
Síndrome de Kartagener , Adolescente , Brasil/epidemiologia , Cílios , Humanos , Síndrome de Kartagener/diagnóstico , Síndrome de Kartagener/genética , Síndrome de Kartagener/patologia , Microscopia Eletrônica de Transmissão , Centros de Atenção TerciáriaRESUMO
Primary ciliary dyskinesia (PCD) is a rare genetic disease that produces functional and structural de fects in the cilia. In Peru, no cases of this disease have been reported in the pediatric population. OBJECTIVE: To describe the clinical, radiological and ciliary ultrastructure characteristics in children with PCD, in a country with medium economic resources. CLINICAL CASE: We report 5 patients with PCD treated at the Instituto Nacional de Salud del Niño-Breña (Peru). Age range 1 to 5 years (median 3 years). Three patients were male. The most frequent clinical manifestations were chronic wet cough, rhonchi, coarse crackles, recurrent bronchial obstructive syndrome, and recurrent pneumonia. All patients had atelectasis, three had bronchiectasis, and two had dextrocardia with situs inversus. Two patients had undergone lobectomy. Other causes of recurrent pneumonias were ruled out with im munodeficiency study, chlorine test and pulmonary aspiration The electron microscopy showed ab sence of the inner arm of dynein as the most frequent pattern. All patients received treatment with antibiotics, nebulization with hypertonic saline, and respiratory physiotherapy with good adherence. CONCLUSION: In medium incomes countries, electron microscopy associated with clinical and radio logical characteristics plays an important role in the early diagnosis of this disease. This is the first Peruvian report that contributes to the casuistry and epidemiology of this rare pathology.
Assuntos
Síndrome de Kartagener , Humanos , Criança , Masculino , Lactente , Pré-Escolar , Feminino , Síndrome de Kartagener/diagnóstico , Síndrome de Kartagener/terapia , Síndrome de Kartagener/genética , Microscopia Eletrônica , Cílios/ultraestrutura , Brônquios , Diagnóstico PrecoceRESUMO
Kartagener's syndrome is a subset of primary ciliary dyskinesia, an autosomal recessive inherited disease, and is characterized by the triad of chronic sinusitis, bronchiectasis, and situs inversus. This paper reports the case of a 27-year-old female presenting with dyspnea on medium exertion, accompanied by chronic cough, non-productive or with clear expectoration. She had recurrent pneumonia until 15 years of age and underwent a lobectomy in the lower lobe of the left lung, probably due to bronchiectasis. Chest computed tomography showed situs inversus totalis, signs of previous surgical manipulation, and mild bronchial thickening. Computed tomography of the paranasal sinuses showed signs of chronic sinusitis due to a probable ciliary kinesis disorder. These finding suggest the diagnosis of Kartagener's syndrome. The prognosis reveals a slow rate of decline in lung function. However, repeated or chronic infections can negatively influence the quality of life of these patients.
Assuntos
Humanos , Feminino , Adulto , Situs Inversus/diagnóstico por imagem , Síndrome de Kartagener/complicações , Dextrocardia/diagnóstico , Situs Inversus/complicações , Síndrome de Kartagener/diagnóstico , Transtornos da Motilidade CiliarRESUMO
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.
Assuntos
Humanos , Recém-Nascido , Pré-Escolar , Adulto , Síndrome de Kartagener/diagnóstico , Síndrome de Kartagener/genética , Síndrome de Kartagener/terapia , Cílios/ultraestrutura , Biópsia , Algoritmos , Testes Genéticos , Microscopia de Vídeo , Microscopia Eletrônica de Transmissão , Óxido Nítrico/análiseRESUMO
At present, there is no specific treatment for primary ciliary dyskinesia, nor controlled and randomized clinical trials to determine how the management and monitoring of these patients should be considered. The therapeutic options are extrapolated from other diseases, such as cystic fibrosis, or non-cystic fibrosis bronchiectasis. However, the implementation of specific groups of experts, both in the USA (PDC-foundation) and in Europe (BESTCILIA or BEAT-PD), are helping to increase knowledge of the disease, opening research channels and seeking new treatments. Until we have therapies capable of correcting the basic defect of the disease, the pillars of treatment are the daily cleansing of the airways and aggressive antibiotherapy against respiratory infections. Multidisciplinary care in specialized centers where pulmonary function is monitored and the infection is prevented and treated will improve, as in cystic fibrosis, the results of patients.
En la actualidad no existe un tratamiento específico para la discinesia ciliar primaria, ni se cuenta con ensayos clínicos controlados y randomizados que permitan determinar cómo debe plantearse el manejo y seguimiento de estos pacientes. Las opciones terapéuticas son extrapoladas de otras enfermedades, como la fibrosis quística, o las bronquiectasias no fibrosis quística. Sin embargo, la puesta en marcha de grupos específicos de expertos, tanto en USA (PDC-foundation) como en Europa (BESTCILIA o BEAT-PD), están permitiendo incrementar el conocimiento de la enfermedad, abriendo vías de investigación y buscando nuevos tratamientos. Hasta contar con terapias capaces de corregir el defecto básico de la enfermedad, los pilares del tratamiento son la limpieza diaria de las vías aéreas y la antibioterapia agresiva frente a las infecciones respiratorias. La atención multidisciplinar en centros especializados donde se monitorice la función pulmonar y se prevengan y traten las infecciones mejorará, como en la fibrosis quística, los resultados de los pacientes.
Assuntos
Humanos , Síndrome de Kartagener/diagnóstico , Síndrome de Kartagener/fisiopatologia , Síndrome de Kartagener/genética , Síndrome de Kartagener/terapia , Infecções Respiratórias/tratamento farmacológico , Seguimentos , Pneumopatias/fisiopatologia , Pneumopatias/terapia , Pneumopatias FúngicasRESUMO
Primary ciliary dyskinesia is a rare autosomal recessive disease with compromised mucociliary drainage. Among the most commonly recommended non-pharmacological therapeutic strategies are secretion drainage techniques. However, the evidence for the use and effectiveness of these techniques is low, and they are generally based on extrapolated evidence of cystic fibrosis. This article reviews the recommendations and available evidence of chest physiotherapy, mainly manual and instrumental techniques of bronchial drainage and physical exercise in children with primary ciliary dyskinesia.
La disquinesia ciliar primaria es una enfermedad autosómica recesiva rara con compromiso del drenaje mucociliar. Entre las estrategias terapéuticas no farmacológicas más comúnmente recomendadas se encuentra las técnicas de drenaje de secreciones. Sin embargo, la evidencia del uso y efectividad de estas técnicas es reducida y generalmente se basan en evidencia extrapolada de la fibrosis quística. Este artículo revisa las recomendaciones y la evidencia disponible de la kinesiología respiratoria, principalmente las técnicas manuales e instrumentales de drenaje bronquial y el ejercicio físico en niños con disquinesia ciliar primaria.
Assuntos
Humanos , Lactente , Criança , Adulto , Pneumonia/terapia , Terapia Respiratória/métodos , Síndrome de Kartagener/diagnóstico , Modalidades de Fisioterapia , Exercício Físico/fisiologia , Drenagem/instrumentação , Secreções CorporaisRESUMO
Primary Ciliary Dyskinesia (PCD) is underdiagnosed in Brazil. We enrolled patients from an adult service of Bronchiectasis over a two-year period in a cross-sectional study. The inclusion criteria were laterality disorders (LD), cough with recurrent infections and the exclusion of other causes of bronchiectasis. Patients underwent at least two of the following tests: nasal nitric oxide, ciliary movement and analysis of ciliary immunofluorescence, and genetic tests (31 PCD genes + CFTR gene). The clinical characterization included the PICADAR and bronchiectasis scores, pulmonary function, chronic Pseudomonas aeruginosa (cPA) colonization, exhaled breath condensate (EBC) and mucus rheology (MR). Forty-nine of the 500 patients were diagnosed with definite (42/49), probable (5/49), and clinical (2/49) PCD. Twenty-four patients (24/47) presented bi-allelic pathogenic variants in a total of 31 screened PCD genes. A PICADAR score > 5 was found in 37/49 patients, consanguinity in 27/49, LD in 28/49, and eight PCD sibling groups. FACED diagnosed 23/49 patients with moderate or severe bronchiectasis; FEV1 ≤ 50% in 25/49 patients, eight patients had undergone lung transplantation, four had been lobectomized and cPA+ was determined in 20/49. The EBC and MR were altered in all patients. This adult PCD population was characterized by consanguinity, severe lung impairment, genetic variability, altered EBC and MR.
Assuntos
Síndrome de Kartagener/diagnóstico , Pneumopatias/diagnóstico , Infecções por Pseudomonas/diagnóstico , Adulto , Idoso , Brasil/epidemiologia , Comorbidade , Estudos Transversais , Feminino , Testes Genéticos , Humanos , Síndrome de Kartagener/epidemiologia , Síndrome de Kartagener/genética , Pneumopatias/epidemiologia , Pneumopatias/genética , Masculino , Pessoa de Meia-Idade , Prevalência , Infecções por Pseudomonas/epidemiologia , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/isolamento & purificação , Pseudomonas aeruginosa/fisiologia , Índice de Gravidade de Doença , Adulto JovemRESUMO
Kartagener Syndrome is an inherited autosomal recessive disorder characterized by primary ciliary dyskinesia and the triad of situs inversus viscerum, chronic sinus disease and bronchiectasis. Its prevalence varies from 1/15 000 to 1/30 000 but it is estimated that a lot of patients with primary ciliary dyskinesia have not been diagnosed as such. Its clinical presentation is non-specific and heterogeneous, and there is not a single, gold standard, diagnostic test. The diagnosis is often delayed because of these reasons and limitations and no availability of diagnostic tests. Early diagnosis and treatment change patient's prognosis. In addition, Scientific Societies have published recent diagnostic algorithm to evaluate the patient with suspected primary ciliary dyskinesia. Therefore, it is important to keep up to date with all the latest articles. We present the case of a newborn with this syndrome diagnosed by genetic analysis in a secondary care hospital.
El síndrome de Kartagener es una enfermedad hereditaria autosómica recesiva caracterizada por la asociación de discinesia ciliar primaria y la tríada situs inversus total, sinusitis crónicas y bronquiectasias. Su prevalencia varía en 1/15 000-1/30 000, pero se estima que muchos pacientes con discinesia ciliar primaria no han sido diagnosticados. Su presentación clínica es inespecífica y heterogénea, y no hay una única prueba gold standard para su diagnóstico. Esto, unido a las limitaciones y no disponibilidad de las pruebas, hace que el diagnóstico se retrase. Un diagnóstico y tratamiento adecuados de forma precoz modifican el pronóstico. En los últimos años, las sociedades han publicado algoritmos diagnósticos para pacientes con clínica sugestiva. Por ello, es importante una puesta al día y enfatizar en la necesidad de una sospecha clínica ante las manifestaciones clínicas de esta enfermedad. Se presenta a un recién nacido con este síndrome diagnosticado por estudio genético en un hospital secundario.
Assuntos
Síndrome de Kartagener/diagnóstico , Transtornos da Motilidade Ciliar/diagnóstico , Diagnóstico Diferencial , Feminino , Humanos , Recém-Nascido , Síndrome de Kartagener/genética , Síndrome de Kartagener/fisiopatologiaRESUMO
El fenotipo de BQC y Retinitis Pigmentosa, asociación de defectos en las cilias móviles y sensoriales, podría aportar en este sentido datos valiosos y es importante reconocerlo.