RESUMO
BACKGROUND: Chronic rhinosinusitis (CRS) and bacterial sinusitis are ubiquitous in patients with primary ciliary dyskinesia (PCD). From the sinuses, Pseudomonas aeruginosa can infect the lungs. METHODS: We studied the effect of endoscopic sinus surgery (ESS) on symptoms of CRS and lower airway infections in PCD patients in a prospective single-arm intervention study of ESS with adjuvant therapy using nasal irrigation with saline, topical nasal steroids, and 2 weeks of systemic antibiotics. Additional treatment with local colistin for 6 months was instigated when P. aeruginosa was cultured at ESS. RESULTS: Twenty-four PCD patients underwent ESS to search for an infectious focus (n = 10), due to severe symptoms of CRS (n = 8), or both (n = 6). Bacteria were cultured from sinus samples in 21 patients (88%), and simultaneous sinus and lung colonization with identical pathogens were observed in 13 patients (62%). Four patients with preoperative P. aeruginosa lung colonization (25%) had no regrowth during follow-up; 2 of these had P. aeruginosa sinusitis. Sinonasal symptoms were improved 12 months after ESS and we observed a trend toward better lung function after ESS. CONCLUSION: We demonstrated an improvement in CRS-related symptoms after ESS and adjuvant therapy. In selected PCD patients, the suggested regimen may postpone chronic lung infection with P. aeruginosa and stabilize lung function.
Assuntos
Síndrome de Kartagener/cirurgia , Pólipos Nasais/cirurgia , Seios Paranasais/cirurgia , Infecções por Pseudomonas/prevenção & controle , Rinite/cirurgia , Sinusite/cirurgia , Adolescente , Adulto , Idoso , Antibacterianos/uso terapêutico , Líquido da Lavagem Broncoalveolar/microbiologia , Doença Crônica , Endoscopia , Feminino , Humanos , Síndrome de Kartagener/tratamento farmacológico , Síndrome de Kartagener/microbiologia , Síndrome de Kartagener/fisiopatologia , Pulmão/microbiologia , Pulmão/fisiologia , Masculino , Pessoa de Meia-Idade , Pólipos Nasais/tratamento farmacológico , Pólipos Nasais/microbiologia , Pólipos Nasais/fisiopatologia , Infecções por Pseudomonas/microbiologia , Infecções por Pseudomonas/fisiopatologia , Infecções por Pseudomonas/terapia , Pseudomonas aeruginosa , Qualidade de Vida , Rinite/tratamento farmacológico , Rinite/microbiologia , Rinite/fisiopatologia , Sinusite/tratamento farmacológico , Sinusite/microbiologia , Sinusite/fisiopatologia , Esteroides/uso terapêutico , Irrigação Terapêutica , Adulto JovemRESUMO
BACKGROUND: Clinical management of primary ciliary dyskinesia (PCD) respiratory disease is currently based on improving mucociliary clearance and controlling respiratory infections, through the administration of antibiotics. Treatment practices in PCD are largely extrapolated from more common chronic respiratory disorders, particularly cystic fibrosis, but no randomized controlled trials (RCT) have ever evaluated efficacy and safety of any pharmacotherapeutics used in the treatment of PCD. Maintenance therapy, with the macrolide antibiotic azithromycin, is currently widely used in chronic respiratory diseases including PCD. In addition to its antibacterial properties, azithromycin is considered to have beneficial anti-inflammatory and anti-quorum-sensing properties. The aim of this study is to determine the efficacy of azithromycin maintenance therapy for 6 months on respiratory exacerbations in PCD. The secondary objectives are to evaluate the efficacy of azithromycin on lung function, ventilation inhomogeneity, hearing impairment, and symptoms (respiratory, sinus, ears and hearing) measured on a PCD-specific health-related quality of life instrument, and to assess the safety of azithromycin maintenance therapy in PCD. METHODS: The BESTCILIA trial is a European multi-centre, double-blind, randomized, placebo-controlled, parallel group study. The intervention is tablets of azithromycin 250/500 mg according to body weight or placebo administered three times a week for 6 months. Subjects with a confirmed diagnosis of PCD, age 7-50 years, are eligible for inclusion. Chronic pulmonary infections with Gram-negative bacteria or any recent occurrence of non-tuberculous mycobacteria are exclusion criteria. The planned number of subjects to be included is 125. The trial has been approved by the Research Ethics Committees of the participating institutions. DISCUSSION: We present a study protocol of an ongoing RCT, evaluating for the first time, the efficacy and safety of a pharmacotherapeutic treatment for patients with PCD. The RCT evaluates azithromycin maintenance therapy, a drug already commonly prescribed in other chronic respiratory disorders. Furthermore, the trial will utilize the Lung clearance index and new, PCD-specific quality of life instruments as outcome measures for PCD. Recruitment is hampered by frequent occurrence of Pseudomonas aeruginosa infection, exacerbations at enrolment, and the patients' perception of disease severity and necessity of additional management and treatment during trial participation. TRIAL REGISTRATION: EudraCT 2013-004664-58 (date of registration: 2014-04-08).
Assuntos
Antibacterianos/administração & dosagem , Azitromicina/administração & dosagem , Síndrome de Kartagener/tratamento farmacológico , Projetos de Pesquisa , Infecções Respiratórias/tratamento farmacológico , Adolescente , Adulto , Antibacterianos/efeitos adversos , Azitromicina/efeitos adversos , Criança , Progressão da Doença , Método Duplo-Cego , Europa (Continente) , Feminino , Humanos , Síndrome de Kartagener/complicações , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Análise de Regressão , Espirometria , Resultado do Tratamento , Capacidade Vital , Adulto JovemRESUMO
RATIONALE: Spirometry in children with cystic fibrosis (CF) frequently fails to return to baseline after treatment for a pulmonary exacerbation. It is unclear whether the same is true for children with primary ciliary dyskinesia (PCD). OBJECTIVES: To determine in children with PCD treated with intravenous antibiotics for a pulmonary exacerbation: (1) the proportion who recover to baseline forced expiratory volume at 1 sec (FEV1 ) within 3 months after treatment and (2) to try to identify factors which are associated with failure to regain pre-exacerbation FEV1 . METHODS: Cohort study using the PCD database for children at the Royal Brompton Hospital, 2003-2013. We selected the first pulmonary exacerbation treated with intravenous antibiotics. The best FEV1 within 3 months after treatment was compared to the best FEV1 in the 12 months before treatment (baseline). Recovery to baseline was defined as any FEV1 after treatment that was greater than or equal to 90% of the baseline FEV1 . RESULTS: 32/150 children (21%) had at least one pulmonary exacerbation. 23/30 (77%) regained baseline spirometry within 3 months of treatment. There was no difference between responders and non-responders in any baseline characteristics. CONCLUSIONS: Around 25% of children with PCD fail to recover to baseline lung function within 3 months following treatment for a pulmonary exacerbation, similar to CF. Better treatment strategies are needed, and the results also suggest that prevention of exacerbations would be a useful end-point in clinical trials. Pediatr Pulmonol. 2016;51:1362-1366. © 2016 Wiley Periodicals, Inc.
Assuntos
Antibacterianos/uso terapêutico , Síndrome de Kartagener/fisiopatologia , Pulmão/fisiopatologia , Recuperação de Função Fisiológica , Infecções Respiratórias/tratamento farmacológico , Adolescente , Criança , Estudos de Coortes , Bases de Dados Factuais , Progressão da Doença , Feminino , Volume Expiratório Forçado , Humanos , Síndrome de Kartagener/complicações , Síndrome de Kartagener/tratamento farmacológico , Masculino , Infecções Respiratórias/complicações , Infecções Respiratórias/fisiopatologia , Estudos Retrospectivos , EspirometriaRESUMO
BACKGROUND: Mannose-binding lectin (MBL) plays an important role in innate immunity and has been reported to be associated with the age-related decline in lung function in cystic fibrosis. HYPOTHESIS: MBL polymorphisms are associated with lung function decline in Primary Ciliary Dyskinesia (PCD). METHODS: We performed sputum microbiology, spirometry pre- and post-administration of salbutamol, ciliary motion analysis, ultrastructural assessment of cilia, ciliogenesis in culture, and chest high resolution computed tomography in children with a clinical history of respiratory tract infections and/or presence of bronchiectasis suggestive of PCD or secondary ciliary dyskinesia (SCD). All subjects were evaluated for single nucleotide polymorphisms in the gene encoding MBL-2. RESULTS: The diagnosis of PCD was established in 45 subjects, while in the remaining 53 the diagnosis was SCD. A significant bronchodilator response was observed only in PCD associated with the MBL2-3 genotype, which is known to be associated with low/undetectable MBL serum levels. Also, bronchiectasis severity was significantly greater in subjects with MBL2-3 in both PCD and SCD. No other association was found between MBL genotypes and clinical findings. CONCLUSIONS: MBL plays a relatively minor role as a disease modifier in PCD. A similar finding in SCD supports the likely significance of this result.
Assuntos
Bronquiectasia/etiologia , Síndrome de Kartagener/genética , Lectina de Ligação a Manose/genética , Polimorfismo de Nucleotídeo Único , Adolescente , Bronquiectasia/diagnóstico por imagem , Broncodilatadores/uso terapêutico , Feminino , Genótipo , Humanos , Síndrome de Kartagener/complicações , Síndrome de Kartagener/tratamento farmacológico , Masculino , Radiografia , Índice de Gravidade de DoençaRESUMO
Kartagener's syndrome is a rare autosomal-recessive genetic disease with progressive damage of the respiratory system and situs inversus. Although the management of patients with Kartagener's syndrome remains uncertain and evidence is limited, it is important to follow up these patients with an adequate and shared care system. This report presents a clinical case of Kartagener's syndrome in a 25-year-old woman. Computed tomography showed dextrocardia and bronchiectasis. Abdominal X-ray and ultrasound confirmed situs inversus totalis. After 7 years, good treatment results were achieved: lung function improved and radiological findings showed no changes. The present case discusses the complex interrelationship between the genetic variation and a proper nonspecific management of Kartagener's syndrome.
Assuntos
Síndrome de Kartagener/fisiopatologia , Adulto , Antibacterianos/uso terapêutico , Bronquiectasia/diagnóstico por imagem , Bronquiectasia/etiologia , Broncodilatadores/uso terapêutico , Proteínas de Transporte/genética , Proteínas de Transporte/fisiologia , Terapia Combinada , Progressão da Doença , Suscetibilidade a Doenças , Expectorantes/uso terapêutico , Feminino , Genótipo , Humanos , Imunoglobulina A/análise , Síndrome de Kartagener/diagnóstico por imagem , Síndrome de Kartagener/tratamento farmacológico , Síndrome de Kartagener/genética , Síndrome de Kartagener/terapia , Terapia Respiratória , Infecções Respiratórias/tratamento farmacológico , Infecções Respiratórias/etiologia , Espirometria , Tomografia Computadorizada por Raios XRESUMO
INTRODUCCIÓN: El Síndrome de Kartagener es una enfermedad hereditaria autosómica recesiva, caracterizada por dextrocardia, bronquiectasias, sinusitis crónica e infertilidad; causada por una mutación en el cromosoma 5p, locus de la proteína dineína, componente de cilios de tracto respiratorio y reproductor, lo que resulta en bajo clearance mucociliar y discinesia primaria. La prevalencia es aproximadamente de 1:10.000 individuos. El diagnóstico es clínico con confirmación mediante exámenes de función y estructura ciliar. PRESENTACIÓN DEL CASO: Paciente sexo masculino, 35 años, con antecedente de Síndrome de Kartagener en tratamiento; consulta en Julio de 2011 en Hospital de Lirquén por dolor en la región mamaria izquierda, irradiado a región infraescapular del mismo lado, punzante, intensidad 7/10, comienzo insidioso y tres días de evolución, acompañado de sensación febril, tercianas, diaforesis y tos húmeda con expectoración mucopurulenta. Examen físico: situs inverso en tórax y abdomen. Examen pulmonar: crépitos bilaterales intensificados en base izquierda, estertores difusos y roncus en ambas bases. Examen de extremidades: acropaquia. A través de radiografía de tórax se diagnostica neumonía. Es hospitalizado en el Servicio de Medicina Hombres para manejo con ceftriaxona endovenosa, inmunosupresores y monitoreo. El paciente evolucionó con buena respuesta, por lo que es dado de alta para continuar con antibióticos orales en domicilio. DISCUSIÓN: Las patologías de inmovilidad ciliar afectan el tracto respiratorio y esperma de estos pacientes. Es útil conocer este diagnóstico ya que permitirá buscar y tratar directamente sus complicaciones, además de ayudar al paciente en las consecuencias psicológicas de la infertilidad.
INTRODUCTION: Kartagener Syndrome is an autosomal recessive inherited disease characterized by dextrocardia, bronchiectasias, chronic sinusitis and infertility, caused by a mutation onchoromosome 5p, locus of dynein protein, component of respiratory cilia and reproductive system, resulting in low mucociliar clearance and primary discinesia. The prevalence is 1:10,000. The clinical diagnosis is confirmed by examination of ciliary structure and function. CASE REPORT: Male patient, 35 years old with a history of Kartagener Syndrome in treatment consults in July at Lirquen Hospital for pain in the left breast area, radiating to infrascapular region of the same side, lancing, intensity 7/10, insidious onset and three days duration, accompanied by feeling feverish, diaphoresis, and productive wet cough. Physical exam: situs inversus in the thorax and abdomen. Pulmonary exam: bilateral crepitus intensified in left base, diffuse rales and rhonchi in both bases; Limbs exam: clubbing. Through chest radiograph was diagnosed with pneumonia. Is hospitalized in Men Medicine Service for intravenous ceftriaxone management, inmunosuppresants, and monitoring. The patient has good response to treatment, so it is discharged to continue with oral antibiotics at home. DISCUSSION: The immotile ciliar diseases affect the respiratory tract and sperm of these patients. It helps to know the diagnosis because it will allow search and efficiently treat complications, besides helping the patient in the psychological consequences of infertility. Spirometry is necessary and chest radiography is warranted in this case for evaluation and study of the infectious respiratory disease that the patient debut.
Assuntos
Humanos , Masculino , Adulto , Pneumonia/etiologia , Síndrome de Kartagener/complicações , Síndrome de Kartagener/tratamento farmacológico , Antibacterianos/uso terapêutico , Pneumonia/tratamento farmacológico , Radiografia TorácicaRESUMO
A 46-year-old man was referred to our hospital with hemoptysis. He had been diagnosed with chronic sinusitis since childhood, but had received no treatment. Chest CT showed a diffuse centrilobular granular shadow and thickened bronchial walls. Otitis media and decreased spermatic motor ability were identified. In addition, electron microscopy of a biopsy specimen of the nasal mucosa showed a deficiency of inner dynein. Based on these clinical findings, primary ciliary dyskinesia (PCD) was diagnosed and successfully treated with long-term, low-dose clarithromycin. Although the effects of macrolide therapy remain controversial, long-term treatment with low-dose clarithromycin might confer clinical benefits upon patients with PCD.
Assuntos
Claritromicina/administração & dosagem , Síndrome de Kartagener/diagnóstico , Síndrome de Kartagener/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Resultado do TratamentoRESUMO
Recombinant human DNase (rhDNase) reduces viscosity of sputum. Effect has been documented in cystic fibrosis and postoperatively in paediatric heart disease. Single dose treatment with rhDNase in paediatric asthma has no effect. In respiratory syncytial virus infection, treatment with rhDNase may be associated with increased need for supplemental oxygen. In adults with idiopathic bronchiectasis, treatment with rhDNase leads to more pulmonary exacerbations and a greater decline in pulmonary function tests. There are no controlled studies on rhDNase in primary ciliary dyskinesia or atelectasis.
Assuntos
Desoxirribonuclease I/administração & dosagem , Doenças Respiratórias/tratamento farmacológico , Administração por Inalação , Adulto , Asma/tratamento farmacológico , Bronquiectasia/tratamento farmacológico , Criança , Transtornos da Motilidade Ciliar/tratamento farmacológico , Contraindicações , Humanos , Síndrome de Kartagener/tratamento farmacológico , Complicações Pós-Operatórias/tratamento farmacológico , Atelectasia Pulmonar/tratamento farmacológico , Infecções por Vírus Respiratório Sincicial/tratamento farmacológico , Resultado do TratamentoRESUMO
Primary ciliary dyskinesia (PCD) is a genetic disease associated with abnormal ciliary structure and function, leading to impaired mucociliary clearance, an important primary innate defense mechanism that protects the lungs. Drugs that can effectively treat PCD should overcome the defect in ciliary function and increase the mucociliary clearance. However, there are currently no therapeutic strategies that correct the inborn error of ciliary dysfunction to restore mucociliary clearance. It is unclear if osmolar agents like hypertonic saline or mannitol, therapies that increase the respiratory surface hydration like ion-channel regulators, or therapies aimed at reducing inflammation or mucus production, or softening the mucus will be effective in PCD. Many of these modalities are used in cystic fibrosis, yet no evidence exists to support their routine use in PCD. Newer genetic modifiers show an exciting potential for personalized medication, combining selection of patients with a common genetic mutation and a drug treatment that has been specifically designed to overcome that mutation, and will greatly enhance the therapeutic arsenal for PCD. This review summarizes current and future prospects for these therapeutic options.
Assuntos
Antibacterianos/uso terapêutico , Fibrose Cística/tratamento farmacológico , Desoxirribonuclease I/uso terapêutico , Diuréticos Osmóticos/uso terapêutico , Expectorantes/uso terapêutico , Soluções Hipertônicas/uso terapêutico , Síndrome de Kartagener/tratamento farmacológico , Humanos , Síndrome de Kartagener/genética , Depuração Mucociliar/efeitos dos fármacos , Mutação/efeitos dos fármacos , Proteínas Recombinantes , Resultado do TratamentoRESUMO
Primary ciliary dyskinesia (PCD) is a rare genetic disease, in which a number of human organs are involved: upper and lower respiratory tract, spermatozoa in males and fallopian tube in females. In minority of cases PCD presents as Kartagener's syndrome (KS): sinusitis, bronchiectasis and inversion of internal organs. We report a case of Kartagener's syndrome in 43-year-old fertile male. After clinical and radiological examination and biopsy of the bronchial mucosa diagnosis of KS was established. The problem of fertility in KS males is discussed.
Assuntos
Síndrome de Kartagener/diagnóstico , Adulto , Diagnóstico Diferencial , Humanos , Infertilidade Masculina/etiologia , Síndrome de Kartagener/tratamento farmacológico , Masculino , Fatores de Tempo , Resultado do TratamentoRESUMO
The association of diffuse bronchiolitis in patients with Kartagener's syndrome (KS) has not been reported previously. The aim of this study was to present the morphological characteristics of bronchiolitis in patients with KS. Eight patients (four males, four females; mean age 37.9+/-18.7 yrs), clinically diagnosed as KS with the classical triad of chronic pansinusitis, bronchiectasis and situs in versus with dextrocardia, were evaluated. Routine chest radiography showed bronchiectasis and dextrocardia in all patients. Chest computed tomography (CT) showed diffuse centrilobular small nodules up to 2 mm in diameter throughout both lungs in six out of eight patients. Pulmonary function tests revealed marked obstructive impairment in all patients (forced expiratory volume in one second 57.0+/-11.3%, residual volume/total lung capacity 45.+/-12.7%, maximum midexpiratory flow 0.92+/-0.72 L x s(-1), forced vital capacity 74.1+/-12.2% (all mean +/- SD)). The examination of cilial movement of the bronchus revealed immotility in all of the five patients examined. The ultrastructure showed ciliary dynein arm defects in all patients. Histopathological examination of lung specimens obtained at autopsy or by video-assisted thoracoscopic surgery showed obliterative thickening of the walls of the membranous bronchioli with infiltration of lymphocytes, plasma cells and neutrophils, but most of the distal respiratory bronchioli were spared and alveolar spaces were overinflated. Pathologically, the diffuse centrilobular small nodules on the chest CT mainly corresponded to membranous bronchiolitis. This is the first report demonstrating that the association of diffuse bronchiolitis might be one of the characteristic features of the lung in Kartagener's syndrome.
Assuntos
Infecções Bacterianas/diagnóstico , Bronquiolite/diagnóstico , Síndrome de Kartagener/diagnóstico , Pulmão/patologia , Adolescente , Adulto , Idoso , Antibacterianos , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/microbiologia , Biópsia , Bronquiolite/tratamento farmacológico , Bronquiolite/microbiologia , Diagnóstico Diferencial , Quimioterapia Combinada/uso terapêutico , Feminino , Humanos , Síndrome de Kartagener/tratamento farmacológico , Pulmão/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Prognóstico , Testes de Função Respiratória , Escarro/microbiologia , Toracoscopia , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
In 25 children with damaged mucociliary function of the nasal mucosa the authors used local ATP treatment. It was found that ATP solution applied to the nasal mucosa improves mucociliary function and reduces the transport time to normal; in acute, relapsing and allergic rhinosinusitis, in Kartagener's syndrome it improves partially the function of cilia, while transport remains prolonged. It seems that local application of ATP in drops may have a favourable effect on rhinosinusitis and prevent relapses.
Assuntos
Trifosfato de Adenosina/uso terapêutico , Depuração Mucociliar/efeitos dos fármacos , Hipersensibilidade Respiratória/tratamento farmacológico , Sinusite/tratamento farmacológico , Doença Aguda , Criança , Humanos , Síndrome de Kartagener/tratamento farmacológico , Síndrome de Kartagener/fisiopatologia , Sinusite/fisiopatologiaRESUMO
Recent experimental studies have demonstrated extensive biochemical differences between the outer and inner dynein arms of cilia. The inner dynein arms are now emerging as the "prime movers" for ciliary clearance. We studied ciliary motility as evidenced by radioisotope mucociliary clearance, and the ultrastructure of respiratory cilia in a patient with Kartagener's syndrome. Cilia exhibited complete absence of only the inner dynein arms, while retaining outer arms, and mucociliary clearance was totally absent. We also studied neutrophil chemotaxis and other immunologic functions in our patient and found them to be normal. Our findings demonstrate an association between the structural abnormality of absent inner dynein arms alone and ciliary immotility in Kartagener's syndrome. The neutrophil migration abnormalities may have a different mechanism which needs further study.