RESUMO
PURPOSE: Primary ciliary dyskinesia (PCD) is a heterogeneous disorder that includes respiratory symptoms, laterality defects, and infertility caused by dysfunction of motile cilia. Most PCD-causing variants result in abnormal outer dynein arms (ODAs), which provide the generative force for respiratory ciliary beating and proper mucociliary clearance. METHODS: In addition to studies in mouse and planaria, clinical exome sequencing and functional analyses in human were performed. RESULTS: In this study, we identified homozygous pathogenic variants in CLXN (EFCAB1/ODAD5) in 3 individuals with laterality defects and respiratory symptoms. Consistently, we found that Clxn is expressed in mice left-right organizer. Transmission electron microscopy depicted ODA defects in distal ciliary axonemes. Immunofluorescence microscopy revealed absence of CLXN from the ciliary axonemes, absence of the ODA components DNAH5, DNAI1, and DNAI2 from the distal axonemes, and mislocalization or absence of DNAH9. In addition, CLXN was undetectable in ciliary axonemes of individuals with defects in the ODA-docking machinery: ODAD1, ODAD2, ODAD3, and ODAD4. Furthermore, SMED-EFCAB1-deficient planaria displayed ciliary dysmotility. CONCLUSION: Our results revealed that pathogenic variants in CLXN cause PCD with defects in the assembly of distal ODAs in the respiratory cilia. CLXN should be referred to as ODA-docking complex-associated protein ODAD5.
Assuntos
Cílios , Síndrome de Kartagener , Humanos , Animais , Camundongos , Cílios/genética , Síndrome de Kartagener/genética , Síndrome de Kartagener/metabolismo , Síndrome de Kartagener/patologia , Proteínas de Ligação ao Cálcio , Axonema/genética , Axonema/metabolismo , Axonema/patologia , Mutação , Dineínas do Axonema/genética , Dineínas do Axonema/metabolismoRESUMO
At any age, respiratory manifestations are a major cause of increased morbidity and mortality of inherited metabolic diseases (IMDs). Type and severity are extremely variable, this depending on the type of the underlying disorder. Symptoms and signs originating from upper or lower airways and/or thoracic wall and/or respiratory muscles involvement can occur either at presentation or in the late clinical course. Acute respiratory symptoms can trigger metabolic decompensation which, in turn, makes airway symptoms worse, creating a vicious circle. We have identified 181 IMDs associated with various types of respiratory symptoms which were classified into seven groups according to the type of clinical manifestations affecting the respiratory system: (i) respiratory failure, (ii) restrictive lung disease, (iii) interstitial lung disease, (iv) lower airway disease, (v) upper airway obstruction, (vi) apnea, and (vii) other. We also provided a list of investigations to be performed based on the respiratory phenotypes and indicated the therapeutic strategies currently available for IMD-associated airway disease. This represents the thirteenth issue in a series of educational summaries providing a comprehensive and updated list of metabolic differential diagnoses according to system involvement.
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Doenças Metabólicas , Doenças Respiratórias , Humanos , Doenças Metabólicas/complicações , Doenças Respiratórias/etiologia , Diagnóstico DiferencialRESUMO
Primary ciliary dyskinesia (PCD) presents with symptoms early in life and the disease course may be progressive, but longitudinal data on lung function are scarce. This multinational cohort study describes lung function trajectories in children, adolescents and young adults with PCD. We analysed data from 486 patients with repeated lung function measurements obtained between the age of 6 and 24â years from the International PCD Cohort and calculated z-scores for forced expiratory volume in 1â s (FEV1), forced vital capacity (FVC) and FEV1/FVC ratio using the Global Lung Function Initiative 2012 references. We described baseline lung function and change of lung function over time and described their associations with possible determinants in mixed-effects linear regression models. Overall, FEV1, FVC and FEV1/FVC z-scores declined over time (average crude annual FEV1 decline was -0.07 z-scores), but not at the same rate for all patients. FEV1 z-scores improved over time in 21% of patients, remained stable in 40% and declined in 39%. Low body mass index was associated with poor baseline lung function and with further decline. Results differed by country and ultrastructural defect, but we found no evidence of differences by sex, calendar year of diagnosis, age at diagnosis, diagnostic certainty or laterality defect. Our study shows that on average lung function in PCD declines throughout the entire period of lung growth, from childhood to young adult age, even among patients treated in specialised centres. It is essential to develop strategies to reverse this tendency and improve prognosis.
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Transtornos da Motilidade Ciliar , Humanos , Criança , Adolescente , Adulto Jovem , Adulto , Estudos de Coortes , Capacidade Vital , Volume Expiratório Forçado , PulmãoRESUMO
Primary ciliary dyskinesia (PCD) is characterized by chronic airway disease, male infertility, and randomization of the left/right body axis as a result of defects of motile cilia and sperm flagella. We identified loss-of-function mutations in the open-reading frame C11orf70 in PCD individuals from five distinct families. Transmission electron microscopy analyses and high-resolution immunofluorescence microscopy demonstrate that loss-of-function mutations in C11orf70 cause immotility of respiratory cilia and sperm flagella, respectively, as a result of the loss of axonemal outer (ODAs) and inner dynein arms (IDAs), indicating that C11orf70 is involved in cytoplasmic assembly of dynein arms. Expression analyses of C11orf70 showed that C11orf70 is expressed in ciliated respiratory cells and that the expression of C11orf70 is upregulated during ciliogenesis, similar to other previously described cytoplasmic dynein-arm assembly factors. Furthermore, C11orf70 shows an interaction with cytoplasmic ODA/IDA assembly factor DNAAF2, supporting our hypothesis that C11orf70 is a preassembly factor involved in the pathogenesis of PCD. The identification of additional genetic defects that cause PCD and male infertility is of great importance for the clinic as well as for genetic counselling.
Assuntos
Padronização Corporal , Dineínas/genética , Síndrome de Kartagener/genética , Mutação/genética , Proteínas Nucleares/genética , Cílios/metabolismo , Cílios/ultraestrutura , Dineínas/ultraestrutura , Feminino , Genes Recessivos , Humanos , Mutação com Perda de Função/genética , Masculino , Cauda do Espermatozoide/metabolismoRESUMO
Nuclear-magnetic-resonance (NMR) profiling of exhaled breath condensate (EBC) provides insights into the pathophysiology of bronchiectasis by identifying specific biomarkers. We evaluated whether NMR-based metabolomics discriminates the EBC-derived metabolic phenotypes ("metabotypes") of 41 patients with non-cystic fibrosis (nCF) bronchiectasis of various etiology [24 subjects with Primary Ciliary Dyskinesia (PCD); 17 patients with bronchiectasis not associated with PCD (nCF/nPCD)], who were compared to 17 healthy subjects (HS). NMR was used for EBC profiling, and Orthogonal Projections to Latent Structures with partial least-squares discriminant analysis (OPLS-DA) was used as a classifier. The results were validated by using the EBC from 17 PCD patients not included in the primary analysis. Different statistical models were built, which compared nCF/nPCD and HS, PCD and HS, all classes (nCF/nPCD-PCD-HS), and, finally, PCD and nCF/nPCD. In the PCD-nCF/nPCD model, four statistically significant metabolites were able to discriminate between the two groups, with only a minor reduction of the quality parameters. In particular, for nCF/nPCD, acetone/acetoin and methanol increased by 21% and 18%, respectively. In PCD patients, ethanol and lactate increased by 25% and 28%, respectively. They are all related to lung inflammation as methanol is found in the exhaled breath of lung cancer patients, acetone/acetoin produce toxic ROS that damage lung tissue in CF, and lactate is observed in acute inflammation. Interestingly, a high concentration of ethanol hampers cilia beating and can be associated with the genetic defect of PCD. Model validation with 17 PCD samples not included in the primary analysis correctly predicted all samples. Our results indicate that NMR of EBC discriminates nCF/nPCD and PCD bronchiectasis patients from HS, and patients with nCF/nPCD from those with PCD. The metabolites responsible for between-group separation identified specific metabotypes, which characterize bronchiectasis of a different etiology.
Assuntos
Bronquiectasia/metabolismo , Expiração , Ressonância Magnética Nuclear Biomolecular , Adolescente , Adulto , Biomarcadores/metabolismo , Testes Respiratórios , Criança , Estudos Transversais , Fibrose Cística/metabolismo , Feminino , Humanos , Masculino , Projetos Piloto , Estudos ProspectivosRESUMO
BACKGROUND: Many preschool children develop recurrent respiratory tract infections (RRI). Strategies to prevent RRI include the use of immunomodulators as pidotimod or probiotics, but there is limited evidence of their efficacy on clinical features or on urine metabolic profile. OBJECTIVE: To evaluate whether pidotimod and/or bifidobacteria can reduce RRI morbidity and influence the urine metabolic profile in preschool children. MATERIALS AND METHODS: Children aged 3-6 years with RRI were enrolled in a four-arm, exploratory, prospective, randomized, double-blinded, placebo-controlled trial. Patients were randomly assigned to receive pidotimod plus bifidobacteria, pidotimod plus placebo, bifidobacteria plus placebo or double placebo for the first 10 days of each month over 4 consecutive months. Respiratory symptoms and infections were recorded with a daily diary by parents during the study. Metabolomic analyses on urine samples collected before and after treatment were performed. RESULTS: Compared to placebo, children receiving pidotimod, alone or with bifidobacteria, had more symptom-free days (69 versus 44, pâ¯=â¯0.003; and 65 versus 44, pâ¯=â¯0.02, respectively) and a lower percentage of days with common cold (17% versus 37%, pâ¯=â¯0.005; and 15% versus 37%, pâ¯=â¯0.004, respectively). The metabolomic analysis showed that children treated with Pidotimod (alone or in combination with bifidobacteria) present, respect to children treated with placebo, a biochemical profile characterized by compounds related to the pathway of steroids hormones, hippuric acid and tryptophan. No significant difference in the metabolic profile was found between children receiving bifidobacteria alone and controls. CONCLUSIONS: Preschool children with RRI treated with pidotimod have better clinical outcomes and a different urine metabolomic profile than subjects receiving placebo. Further investigations are needed to clarify the connection between pidotimod and gut microbiome.
Assuntos
Adjuvantes Imunológicos/uso terapêutico , Bifidobacterium , Probióticos/farmacologia , Ácido Pirrolidonocarboxílico/análogos & derivados , Infecções Respiratórias/tratamento farmacológico , Tiazolidinas/uso terapêutico , Criança , Pré-Escolar , Feminino , Humanos , Placebos , Gravidez , Estudos Prospectivos , Ácido Pirrolidonocarboxílico/uso terapêutico , Prova de Trabalho de PartoRESUMO
Bronchiectasis, conventionally defined as irreversible dilatation of the bronchial tree, is generally suspected on a clinical basis and confirmed by means of chest high-resolution computed tomography. Clinical manifestations, including chronic productive cough and endobronchial suppuration with persistent chest infection and inflammation, may deeply affect quality of life, both in children/adolescents and adults. Despite many cases being idiopathic or post-infectious, a number of specific aetiologies have been traditionally associated with bronchiectasis, such as cystic fibrosis (CF), primary ciliary dyskinesia or immunodeficiencies. Nevertheless, bronchiectasis may also develop in patients with bronchial asthma; chronic obstructive pulmonary disease; and, less commonly, rheumatological disorders and inflammatory bowel diseases. Available literature on the development of bronchiectasis in these conditions and on its management is limited, particularly in children. However, bronchiectasis may complicate the clinical course of the underlying condition at any age, and appropriate management requires an integration of multiple skills in a team of complementary experts to provide the most appropriate care to affected children and adolescents. The present review aims at summarizing the current knowledge and available evidence on the management of bronchiectasis in the other conditions mentioned and focuses on the new therapeutic strategies that are emerging as promising tools for improving patients' quality of life.
Assuntos
Asma/epidemiologia , Bronquiectasia , Doenças Inflamatórias Intestinais/epidemiologia , Administração dos Cuidados ao Paciente/métodos , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Doenças Reumáticas/epidemiologia , Adulto , Bronquiectasia/epidemiologia , Bronquiectasia/terapia , Criança , Comorbidade , HumanosRESUMO
Primary ciliary dyskinesia (PCD) has been considered a relatively mild disease, especially compared to cystic fibrosis (CF), but studies on lung function in PCD patients have been few and small.This study compared lung function from spirometry of PCD patients to normal reference values and to published data from CF patients. We calculated z-scores and % predicted values for forced expiratory volume in 1â s (FEV1) and forced vital capacity (FVC) using the Global Lung Function Initiative 2012 values for 991 patients from the international PCD Cohort. We then assessed associations with age, sex, country, diagnostic certainty, organ laterality, body mass index and age at diagnosis in linear regression models. Lung function in PCD patients was reduced compared to reference values in both sexes and all age groups. Children aged 6-9â years had the smallest impairment (FEV1 z-score -0.84 (-1.03 to -0.65), FVC z-score -0.31 (-0.51 to -0.11)). Compared to CF patients, FEV1 was similarly reduced in children (age 6-9â years PCD 91% (88-93%); CF 90% (88-91%)), but less impaired in young adults (age 18-21â years PCD 79% (76-82%); CF 66% (65-68%)). The results suggest that PCD affects lung function from early in life, which emphasises the importance of early standardised care for all patients.
Assuntos
Transtornos da Motilidade Ciliar/fisiopatologia , Pulmão/fisiopatologia , Adolescente , Adulto , Fatores Etários , Índice de Massa Corporal , Criança , Pré-Escolar , Fibrose Cística/fisiopatologia , Feminino , Volume Expiratório Forçado , Humanos , Lactente , Recém-Nascido , Internacionalidade , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Valores de Referência , Estudos Retrospectivos , Fatores Sexuais , Espirometria , Capacidade Vital , Adulto JovemRESUMO
BACKGROUND: The primary goal of asthma management is to achieve disease control for reducing the risk of future exacerbations and progressive loss of lung function. Asthma not responding to treatment may result in significant morbidity. In many children with uncontrolled symptoms, the diagnosis of asthma may be wrong or adherence to treatment may be poor. It is then crucial to distinguish these cases from the truly "severe therapy-resistant" asthmatics by a proper filtering process. Herein we report on four cases diagnosed as difficult asthma, detail the workup that resulted in the ultimate diagnosis, and provide the process that led to the prescription of omalizumab. CASE PRESENTATION: All children had been initially referred because of asthma not responding to long-term treatment with high-dose inhaled steroids, long-acting ß2-agonists and leukotriene receptor antagonists. Definitive diagnosis was severe asthma. Three out four patients were treated with omalizumab, which improved asthma control and patients' quality of life. We reviewed the current literature on the diagnostic approach to the disease and on the comorbidities associated with difficult asthma and presented the perspectives on omalizumab treatment in children and adolescents. Based on the evidence from the literature review, we also proposed an algorithm for the diagnosis of pediatric difficult-to-treat and severe asthma. CONCLUSIONS: The management of asthma is becoming much more patient-specific, as more and more is learned about the biology behind the development and progression of asthma. The addition of omalizumab, the first targeted biological treatment approved for asthma, has led to renewed optimism in the management of children and adolescents with atopic severe asthma.
Assuntos
Antiasmáticos/uso terapêutico , Anticorpos Anti-Idiotípicos/uso terapêutico , Asma/tratamento farmacológico , Omalizumab/uso terapêutico , Asma/diagnóstico , Criança , Pré-Escolar , Humanos , Masculino , Índice de Gravidade de DoençaRESUMO
The diagnosis of primary ciliary dyskinesia is often confirmed with standard, albeit complex and expensive, tests. In many cases, however, the diagnosis remains difficult despite the array of sophisticated diagnostic tests. There is no "gold standard" reference test. Hence, a Task Force supported by the European Respiratory Society has developed this guideline to provide evidence-based recommendations on diagnostic testing, especially in light of new developments in such tests, and the need for robust diagnoses of patients who might enter randomised controlled trials of treatments. The guideline is based on pre-defined questions relevant for clinical care, a systematic review of the literature, and assessment of the evidence using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach. It focuses on clinical presentation, nasal nitric oxide, analysis of ciliary beat frequency and pattern by high-speed video-microscopy analysis, transmission electron microscopy, genotyping and immunofluorescence. It then used a modified Delphi survey to develop an algorithm for the use of diagnostic tests to definitively confirm and exclude the diagnosis of primary ciliary dyskinesia; and to provide advice when the diagnosis was not conclusive. Finally, this guideline proposes a set of quality criteria for future research on the validity of diagnostic methods for primary ciliary dyskinesia.
Assuntos
Cílios/ultraestrutura , Síndrome de Kartagener/diagnóstico , Cílios/patologia , Técnica Delphi , Diagnóstico Diferencial , Europa (Continente) , Imunofluorescência , Testes Genéticos , Humanos , Síndrome de Kartagener/genética , Microscopia Eletrônica de Transmissão , Microscopia de Vídeo , Óxido Nítrico/análise , Literatura de Revisão como Assunto , Sociedades MédicasRESUMO
Chronic respiratory disease can affect growth and nutrition, which can influence lung function. We investigated height, body mass index (BMI), and lung function in patients with primary ciliary dyskinesia (PCD).In this study, based on the international PCD (iPCD) Cohort, we calculated z-scores for height and BMI using World Health Organization (WHO) and national growth references, and assessed associations with age, sex, country, diagnostic certainty, age at diagnosis, organ laterality and lung function in multilevel regression models that accounted for repeated measurements.We analysed 6402 measurements from 1609 iPCD Cohort patients. Height was reduced compared to WHO (z-score -0.12, 95% CI -0.17 to -0.06) and national references (z-score -0.27, 95% CI -0.33 to -0.21) in male and female patients in all age groups, with variation between countries. Height and BMI were higher in patients diagnosed earlier in life (p=0.026 and p<0.001, respectively) and closely associated with forced expiratory volume in 1 s and forced vital capacity z-scores (p<0.001).Our study indicates that both growth and nutrition are affected adversely in PCD patients from early life and are both strongly associated with lung function. If supported by longitudinal studies, these findings suggest that early diagnosis with multidisciplinary management and nutritional advice could improve growth and delay disease progression and lung function impairment in PCD.
Assuntos
Estatura , Índice de Massa Corporal , Transtornos da Motilidade Ciliar/fisiopatologia , Estado Nutricional , Adolescente , Adulto , Distribuição por Idade , Criança , Pré-Escolar , Progressão da Doença , Feminino , Humanos , Lactente , Recém-Nascido , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Valores de Referência , Testes de Função Respiratória , Estudos Retrospectivos , Adulto JovemRESUMO
Recurrent pneumonia (RP), i.e., at least two episodes of pneumonia in one year or three episodes ever with intercritical radiographic clearing of densities, occurs in 7.7%-9% of children with community-acquired pneumonia. In RP, the challenge is to discriminate between children with self-limiting or minor problems, that do not require a diagnostic work-up, and those with an underlying disease. The aim of the current review is to discuss a reasoned diagnostic approach to RP in childhood. Particular emphasis has been placed on which children should undergo a diagnostic work-up and which tests should be performed. A pediatric case series is also presented, in order to document a single centre experience of RP. A management algorithm for the approach to children with RP, based on the evidence from a literature review, is proposed. Like all algorithms, it is not meant to replace clinical judgment, but it should drive physicians to adopt a systematic approach to pediatric RP and provide a useful guide to the clinician.
Assuntos
Pneumonia/diagnóstico , Pneumonia/epidemiologia , Adolescente , Fatores Etários , Criança , Pré-Escolar , Infecções Comunitárias Adquiridas/diagnóstico , Infecções Comunitárias Adquiridas/epidemiologia , Infecções Comunitárias Adquiridas/etiologia , Comorbidade , Gerenciamento Clínico , Feminino , Humanos , Lactente , Recém-Nascido , Itália/epidemiologia , Masculino , Pneumonia/etiologia , Recidiva , Fatores de RiscoRESUMO
Primary ciliary dyskinesia (PCD) is a rare autosomal recessive disorder leading to chronic upper and lower airway disease. Fundamental data on epidemiology, clinical presentation, course and treatment strategies are lacking in PCD. We have established an international PCD registry to realise an unmet need for an international platform to systematically collect data on incidence, clinical presentation, treatment and disease course.The registry was launched in January 2014. We used internet technology to ensure easy online access using a web browser under www.pcdregistry.eu. Data from 201 patients have been collected so far. The database is comprised of a basic data form including demographic and diagnostic information, and visit forms designed to monitor the disease course.To establish a definite PCD diagnosis, we used strict diagnostic criteria, which required two to three diagnostic methods in addition to classical clinical symptoms. Preliminary analysis of lung function data demonstrated a mean annual decline of percentage predicted forced expiratory volume in 1â s of 0.59% (95% CI 0.98-0.22).Here, we present the development of an international PCD registry as a new promising tool to advance the understanding of this rare disorder, to recruit candidates for research studies and ultimately to improve PCD care.
Assuntos
Síndrome de Kartagener/diagnóstico , Síndrome de Kartagener/epidemiologia , Sistema de Registros , Adolescente , Adulto , Distribuição por Idade , Idoso , Criança , Pré-Escolar , Progressão da Doença , Europa (Continente) , Feminino , Volume Expiratório Forçado , Humanos , Incidência , Lactente , Internet , Colaboração Intersetorial , Masculino , Pessoa de Meia-Idade , América do Norte , Seleção de Pacientes , Adulto JovemRESUMO
BACKGROUND AND OBJECTIVE: Sleep-disordered breathing (SDB) may develop in primary ciliary dyskinesia (PCD), leading to these diseases worsening one another. METHODS: Sixteen stable PCD patients (4.9-17.2 years) and 42 controls underwent overnight respiratory polysomnography (rPSG) and Sleep Disturbances Scale for Children (SDSC). In PCD we assessed nasal endoscopy, pulmonary function tests and chest high-resolution computed tomography (HRCT). RESULTS: Compared with controls, PCD had higher obstructive apnoea (4.7 vs 0.2, P < 0.001), central apnoea (0.8 vs 0.2, P < 0.001), hypopnoea (1.8 vs 0.2, P < 0.001), apnoea-hypopnoea (7.8 vs 0.6, P < 0.001), oxygen desaturation indexes (ODI; 0.7 vs 0.2, P = 0.002), and mean oxygen desaturation (4% vs 1%, P < 0.001), while mean and nadir oxygen saturation (97.1% vs 98.1, P < 0.001) (93% vs 97.2%, P < 0.001) were lower, respectively. In PCD, SDSC was unrelated to rPSG (P > 0.05), with total score and subscores of disorders in initiating and maintaining sleep, and sleep-wake transition lower than controls. PCD patients had chronic rhinosinusitis (100%) and adenoidal hypertrophy (50%). Total HRCT score was 7 (range 0-14). ODI correlated with functional residual capacity (r = 0.8, P = 0.02), total HRCT (r = 0.6, P = 0.03) and peribronchial thickening scores (r = 0.7, P = 0.02). Oxygen saturation was associated with bronchiectasis severity score (r = -0.6, P = 0.02). CONCLUSIONS: PCD's parents may underestimate SDB. As nocturnal desaturation is associated with lung function and structure abnormalities, SDB may significantly contribute to pulmonary morbidity.
Assuntos
Síndrome de Kartagener , Síndromes da Apneia do Sono , Adulto , Criança , Informação de Saúde ao Consumidor , Estudos Transversais , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Itália/epidemiologia , Síndrome de Kartagener/complicações , Síndrome de Kartagener/diagnóstico , Síndrome de Kartagener/epidemiologia , Síndrome de Kartagener/fisiopatologia , Masculino , Mães/educação , Mães/psicologia , Polissonografia/métodos , Estudos Prospectivos , Testes de Função Respiratória/métodos , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença , Síndromes da Apneia do Sono/diagnóstico , Síndromes da Apneia do Sono/epidemiologia , Síndromes da Apneia do Sono/etiologia , Síndromes da Apneia do Sono/fisiopatologia , Síndromes da Apneia do Sono/psicologia , Tomografia Computadorizada por Raios X/métodosRESUMO
PURPOSE: A sensitive imaging technique that assesses ataxia telangiectasia (AT) lung disease without ionizing radiation is highly desirable. We designed a study to evaluate lung changes using magnetic resonance imaging (MRI), and to investigate the relationships among severity and extent of pulmonary abnormalities and clinical, microbiological and functional data in children and young adults with AT. METHODS: Fifteen AT patients (age, 11.3 years; range, 6-31) underwent 3.0-T MRI, spirometry, and deep throat or sputum culture. Images were scored using a modified Helbich score. RESULTS: Although only 8 patients (53 %) had recurrent/chronic respiratory symptoms, MRI identified lung abnormalities in all. Bronchiectasis, peribronchial thickening, mucous plugging, and collapse/consolidation were present in 60 %, 87 %, 67 %, and 13 % of cases, respectively, with no difference between subjects with or without respiratory symptoms. No difference in changes of specific scores was found between the two groups, but the total MRI score was higher in patients with respiratory symptoms (6.5 versus 5, respectively; p = 0.02). Total or specific MRI scores were not associated with patients' age. Of all scores, only mucous plugging subscore appeared significantly related to FEV1 (r = 0.7, p = 0.04) and FEF25-75% (r = 0.9, p = 0.001). MRI scores from patients with positive (n = 5) or negative (n = 10) sputum culture were not significantly different. CONCLUSIONS: MRI is valuable in the assessment of extent and severity of pulmonary changes in children and adults with AT. It represents an helpful tool for the longitudinal evaluation of patients and may be also used as an outcome surrogate to track the effects of medications.
Assuntos
Ataxia Telangiectasia/diagnóstico , Bronquiectasia/diagnóstico , Pulmão/patologia , Imageamento por Ressonância Magnética , Adolescente , Adulto , Ataxia Telangiectasia/fisiopatologia , Bronquiectasia/fisiopatologia , Criança , Progressão da Doença , Estudos de Viabilidade , Feminino , Humanos , Pulmão/diagnóstico por imagem , Masculino , Muco/metabolismo , Cintilografia , Testes de Função Respiratória , Adulto JovemRESUMO
COVID-19 pandemics is rapidly changing. In this article, we review progresses published in the Italian Journal of Pediatrics in 2022. More data on clinical pictures, prevention strategies and active management in children have been provided. The continued evolution of knowledge has driven transformations in the clinical approach to the disease and allowed key advancements in the care of children with COVID-19.
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COVID-19 , Criança , Humanos , COVID-19/epidemiologia , SARS-CoV-2 , Pandemias/prevenção & controle , Itália/epidemiologiaRESUMO
Neuromuscular disease (NMDs) encompass a heterogeneous group of genetic disorders, with respiratory problems of variable intensity and progression described at any pediatric age, from infancy to adolescence, and they are largely associated with significant lifelong morbidity and high mortality. Restriction of breathing, impaired gas exchange, decline of lung function and sleep disordered breathing progressively develop because of muscular weakness and culminate in respiratory failure. Depending on the disease progression, airways manifestations can take weeks to months or even years to evolve, thus depicting two major respiratory phenotypes, characterized by rapid or slow progression to respiratory failure. Assessing type and age at onset of airways problems and their evolution over time can support pediatricians in the diagnostic assessment of NMD. In addition, knowing the characteristics of patients' respiratory phenotype can increase the level of awareness among neonatologists, geneticists, neurologists, pulmonologists, nutritionists, and chest therapists, supporting them in the challenging task of the multidisciplinary medical care of patients. In this review we examine the issues related to the pediatric respiratory phenotypes of NMD and present a novel algorithm that can act as a guide for the diagnostic agenda and the key preventive or therapeutic interventions of airways manifestations. With prolonged survival of children with NMD, the advent of neuromuscular respiratory medicine, including accurate assessment of the respiratory phenotype, will help physicians to determine patients' prognoses and to design studies for the evaluation of new therapies.
Assuntos
Doenças Neuromusculares , Insuficiência Respiratória , Humanos , Doenças Neuromusculares/diagnóstico , Doenças Neuromusculares/terapia , Insuficiência Respiratória/diagnóstico , Insuficiência Respiratória/etiologia , Insuficiência Respiratória/terapia , Taxa Respiratória , PediatrasRESUMO
Obstructive sleep-disordered breathing (SDB) has significant impacts on health, and therefore, a timely and accurate diagnosis is crucial for effective management and intervention. This narrative review provides an overview of the current approaches utilised in the diagnosis of SDB in children. Diagnostic methods for SDB in children involve a combination of clinical assessment, medical history evaluation, questionnaires, and objective measurements. Polysomnography (PSG) is the diagnostic gold standard. It records activity of brain and tibial and submental muscles, heart rhythm, eye movements, oximetry, oronasal airflow, abdominal and chest movements, body position. Despite its accuracy, it is a time-consuming and expensive tool. Respiratory polygraphy instead monitors cardiorespiratory function without simultaneously assessing sleep and wakefulness; it is more affordable than PSG, but few paediatric studies compare these techniques and there is optional recommendation in children. Nocturnal oximetry is a simple and accessible exam that has high predictive value only for children at high risk. The daytime nap PSG, despite the advantage of shorter duration and lower costs, is not accurate for predicting SDB. Few paediatric data support the use of home testing during sleep. Finally, laboratory biomarkers and radiological findings are potentially useful hallmarks of SDB, but further investigations are needed to standardise their use in clinical practice.
RESUMO
The last year saw intensive efforts to advance knowledge in pediatric medicine. This review highlights important publications that have been issued in the Italian Journal of Pediatrics in 2022. We have chosen papers in the fields of allergy, anesthesiology, cardiology, dermatology, endocrinology, gastroenterology, genetics, global health, infectious diseases, metabolism, neonatology, neurology, oncology, pulmonology. Novel valuable developments in epidemiology, pathophysiology, prevention, diagnosis and treatment that can rapidly change the approach to diseases in childhood have been included and discussed.
Assuntos
Anestesiologia , Cardiologia , Doenças Transmissíveis , Dermatologia , Gastroenterologia , Hipersensibilidade , Neonatologia , Neurologia , Pneumologia , Humanos , Criança , Saúde Global , PediatrasRESUMO
INTRODUCTION: Cervical cancer is the fourth most common cancer in women, and its prevention is based on vaccination and screening. Screening consists of molecular human papillomavirus (HPV) testing and cytologic analysis of cervical smears, which require expensive equipment and the interaction of numerous professionals such as biologists, cytologists, laboratory technicians, and pathologists. MATERIALS AND METHODS: We centralize the cervical samples from more than 51 clinics in 1 main laboratory, where automated HPV testing is performed. HPV-positive cases are collected and used to prepare a liquid-based cytology slide, which is stained and immediately scanned. The resulting whole-slide images (WSIs) are immediately available in a remote laboratory where they are examined by experienced cytologists using virtual microscopy. This setup was validated by making each of the 3 readers independently diagnose 506 specimens in random order, using both conventional light microscopy (CLM) and WSIs, with a minimum wash-out period of 3 weeks and with a final discussion for all cases. RESULTS: Intraobserver agreement among CLM and WSI ranged from 0.71 to 0.79, and interobserver agreement for the 3 readers compared with the consensus diagnosis was similar for the 2 modes of assessment. Readers subjectively felt confident in their WSI diagnosis for inadequate and negative cases, but less so in other cases. The perceived difficulty was slightly higher in WSI readings. CONCLUSIONS: Interobserver agreement in cervicovaginal cytology is moderate and does not vary if the slides are examined conventionally or digitally. Despite higher reported subjective difficulty and lower confidence in the WSI diagnosis, we did not observe a deterioration in diagnostic performance using WSI compared with CLM.