RESUMEN
INTRODUCTION: Interstitial lung disease in children (chILD) are rare and mostly severe lung diseases. Very few epidemiological data are available in limited series of patients. The aim of this study was to assess the prevalence and incidence of chILD in France. METHODS: We performed within the RespiRare network a multicentre retrospective observational study in patients with chILD from 2000 to 2022 and a prospective evaluation of chILD's incidence between February 2022 and 2023. RESULTS: chILD was reported in 790 patients in 42 centres. The estimated 2022 prevalence in France was 44 /million children (95% CI 40.76 to 47.46) and the computed incidence was 4.4 /million children (95% CI 3.44 to 5.56). The median age at diagnosis was 3 months with 16.9% of familial forms. Lung biopsy and genetic analyses were performed in 23.4% and 76.9%, respectively. The most frequent chILD aetiologies in the <2 years group were surfactant metabolism disorders (16.3%) and neuroendocrine cell hyperplasia of infancy (11.8%), and in the 2-18 years group diffuse alveolar haemorrhage (12.2%), connective tissue diseases (11.4%), hypersensitivity pneumonitis (8.8%) and sarcoidosis (8.8%). The management included mainly oxygen therapy (52%), corticosteroid pulses (56%), oral corticosteroids (44%), azithromycin (27.2%), enteral nutrition (26.9%), immunosuppressants (20.3%) and hydroxychloroquine (15.9%). The 5-year survival rate was 57.3% for the patients diagnosed before 2 years and 86% between 2 and 18 years. CONCLUSION: This large and systematic epidemiological study confirms a higher incidence and prevalence of chILD than previously described. In order to develop international studies, efforts are still needed to optimise the case collection and to harmonise diagnostic and management practices.
Asunto(s)
Enfermedades Pulmonares Intersticiales , Humanos , Francia/epidemiología , Enfermedades Pulmonares Intersticiales/epidemiología , Enfermedades Pulmonares Intersticiales/diagnóstico , Enfermedades Pulmonares Intersticiales/terapia , Femenino , Masculino , Niño , Preescolar , Adolescente , Incidencia , Estudios Retrospectivos , Lactante , Prevalencia , Estudios ProspectivosRESUMEN
BACKGROUND: It is unclear whether sensitization patterns differentiate children with severe recurrent wheeze (SRW)/severe asthma (SA) from those with non-severe recurrent wheeze (NSRW)/non-severe asthma (NSA). Our objective was to determine whether sensitization patterns can discriminate between children from the French COBRAPed cohort with NSRW/NSA and those with SRW/SA. METHODS: IgE to 112 components (c-sIgE) (ImmunoCAP® ISAC) were analyzed in 125 preschools (3-6 years) and 170 school-age children (7-12 years). Supervised analyses and clustering methods were applied to identify patterns of sensitization among children with positive c-sIgE. RESULTS: We observed c-sIgE sensitization in 51% of preschool and 75% of school-age children. Sensitization to house dust mite (HDM) components was more frequent among NSRW than SRW (53% vs. 24%, p < .01). Sensitization to non-specific lipid transfer protein (nsLTP) components was more frequent among SA than NSA (16% vs. 4%, p < .01) and associated with an FEV1/FVC < -1.64 z-score. Among sensitized children, seven clusters with varying patterns were identified. The two broader clusters identified in each age group were characterized by "few sensitizations, mainly to HDM." One cluster (n = 4) with "multiple sensitizations, mainly to grass pollen, HDM, PR-10, and nsLTP" was associated with SA in school-age children. CONCLUSIONS: Although children with wheeze/asthma display frequent occurrences and high levels of sensitization, sensitization patterns did not provide strong signals to discriminate children with severe disease from those with milder disease. These results suggest that the severity of wheeze/asthma may depend on both IgE- and non-IgE-mediated mechanisms.
Asunto(s)
Alérgenos , Asma , Niño , Preescolar , Animales , Humanos , Inmunoglobulina E , Asma/diagnóstico , Asma/epidemiología , Pyroglyphidae , Dermatophagoides pteronyssinus , Ruidos RespiratoriosRESUMEN
BACKGROUND: A major breakthrough in cystic fibrosis (CF) therapy was achievedAQ1 with CFTR modulators. The lumacaftor/ivacaftor combination is indicated for the treatment of CF in pediatric patients above 6 years old. Pharmacokinetic (PK) studies of lumacaftor/ivacaftor in these vulnerable pediatric populations are AQ2crucial to optimize treatment protocols. OBJECTIVES AND METHODS: The objectives of this study were to describe the population PK (PPK) of lumacaftor and ivacaftor in children with CF, and to identify factors associated with interindividual variability. The association between drug exposure and clinical response was also investigated. RESULTS: A total of 75 children were included in this PPK study, with 191 concentrations available for each compound and known metabolites (lumacaftor, ivacaftor, ivacaftor-M1, and ivacaftor-M6). PPK analysis was performed using Monolix software. A large interindividual variability was observed. The main sources of interpatient variability identified were patient bodyweight and hepatic function (aspartate aminotransferase). Forced expiratory volume in the first second (FEV1) was statistically associated with the level of exposure to ivacaftor after 48 weeks of treatment. CONCLUSIONS: This study is the first analysis of lumacaftor/ivacaftor PPK in children with CF. These data suggest that dose adjustment is required after identifying variability factors to optimize efficacy. The use of therapeutic drug monitoring as a basis for dose adjustment in children with CF may be useful.
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Benzodioxoles , Fibrosis Quística , Quinolonas , Humanos , Niño , Fibrosis Quística/tratamiento farmacológico , Fibrosis Quística/genética , Regulador de Conductancia de Transmembrana de Fibrosis Quística/genética , Regulador de Conductancia de Transmembrana de Fibrosis Quística/uso terapéutico , Combinación de Medicamentos , Aminofenoles/uso terapéutico , Aminopiridinas/uso terapéutico , Volumen Espiratorio ForzadoRESUMEN
OBJETIVOS: Revisar os trabalhos publicados sobre os principais aspectos da bronquiolite obliterante pós-infecciosa, relacionados com sua história, etiologia, epidemiologia, fatores de risco, patogenia, alterações histológicas, manifestações clínicas, exames complementares, critérios diagnósticos, diagnóstico diferencial, tratamento e prognóstico. FONTES DOS DADOS: Realizou-se uma revisão não sistemática nas bases de dados MEDLINE e LILACS, selecionando-se 66 referências mais relevantes. SÍNTESE DOS DADOS: Na bronquiolite obliterante pós-infecciosa ocorre lesão do epitélio respiratório, e a gravidade clínica está relacionada aos diferentes graus de lesão e ao processo inflamatório. O diagnóstico baseia-se no quadro clínico, na exclusão dos principais diagnósticos diferenciais e no auxílio dos exames complementares. A tomografia computadorizada de alta resolução, principalmente com imagens em inspiração e expiração, possibilta a avaliação das pequenas vias aéreas. As provas de função pulmonar caracterizam-se por padrão obstrutivo fixo com redução acentuada do FEF25-75 por cento. O tratamento não está bem estabelecido, e o uso de corticoides tem sido preconizado em forma de pulsoterapia ou por via inalatória em elevadas doses, no entanto, os dados da literatura a respeito de sua eficácia ainda são escassos. O prognóstico a longo prazo é variável, podendo haver melhora clínica ou evolução para insuficiência respiratória crônica e óbito. CONCLUSÃO: A bronquiolite obliterante pós-infecciosa é uma doença que cursa com elevada morbidade e deve ser abordada por equipe multidisciplinar com acompanhamento em longo prazo.
OBJECTIVES: To review publications about the main features of post-infectious bronchiolitis obliterans and its history, etiology, epidemiology, risk factors, pathogenesis, histological findings, clinical presentation, complementary tests, diagnostic criteria, differential diagnosis, treatment and prognosis. SOURCES: Non-systematic review of MEDLINE and LILACS databases and selection of 66 most relevant studies. SUMMARY OF THE FINDINGS: In the post-infectious bronchiolitis obliterans there is an insult to respiratory epithelial cells, and its clinical severity is associated with the degree of lesion and inflammation. Diagnosis is made according to clinical signs and symptoms, by exclusion of main differential diagnoses and with the aid of complementary tests. High resolution CT, particularly images obtained during inspiration and expiration, provide information for the evaluation of the small airways. Pulmonary function tests show fixed airway obstructions and marked decrease of FEF25-75 percent. Treatment has not been definitely established, and corticoids have been administered as pulse therapy or by inhalation of high doses of steroids. However, data about its efficacy are scarce in the literature. Long-term prognosis is variable, and there might be either clinical improvement or deterioration into respiratory insufficiency and death. CONCLUSION: Post-infectious bronchiolitis obliterans is a disease with a high morbidity rate; it should be treated by a multidisciplinary team, and patients should be followed up for a long period of time.
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Niño , Humanos , Bronquiolitis Obliterante/diagnóstico , Infecciones Bacterianas/complicaciones , Bronquiolitis Obliterante/tratamiento farmacológico , Bronquiolitis Obliterante/etiología , Pronóstico , Factores de Riesgo , Virosis/complicacionesRESUMEN
Este estudo teve como objetivo rever a literatura existente sobre a celularidade do LBA em crianças e adolescentes saudáveis, bem como sobre sua utilização como método propedêutico e de acompanhamento nas afecções pulmonares neste grupo etário. Para tanto, utilizamos o banco de dados médico Medline com a seleção de artigos publicados entre 1989 e 2009 utilizando os seguintes descritores MeSH com operadores boolianos: bronchoalveolar lavage AND cytology OR cell AND child. Em crianças saudáveis, a celularidade é composta por macrófagos alveolares (> 80 por cento), linfócitos (cerca de 10 por cento), neutrófilos (cerca de 2 por cento) e eosinófilos (< 1 por cento). O perfil celular sofre alterações de acordo com a doença estudada. Ocorre uma elevação no número de neutrófilos em sibilantes, especialmente os não atópicos, bem como em indivíduos com quadros infecciosos e inflamatórios pulmonares, incluindo fibrose cística e doenças intersticiais pulmonares. Os eosinófilos se elevam em crianças/adolescentes com asma e podem atingir níveis acentuados na aspergilose broncopulmonar alérgica e nas síndromes hipereosinofílicas. A elevação dos linfócitos pode ocorrer em um grupo heterogêneo de doenças. Conclui-se que a celularidade do líquido de LBA, juntamente com dados clínicos e de imagem, tem se mostrado um instrumento essencial de investigação de diversas afecções pulmonares. O LBA possui uma grande utilidade clínica e é menos invasivo que a biópsia pulmonar transbrônquica e a céu aberto. Estudos sobre a celularidade normal do líquido de LBA utilizando-se protocolos internacionalmente padronizados e em diversas faixas etárias para a verificação de valores de referência são necessários para a interpretação mais acurada de resultados em crianças e adolescentes com pneumopatias.
The objective of this study was to review the literature on bronchoalveolar lavage fluid cell profiles in healthy children and adolescents, as well as on the use of BAL as a diagnostic and follow-up tool for lung disease patients in this age bracket. To that end, we used the Medline database, compiling studies published between 1989 and 2009 employing the following MeSH descriptors (with Boolean operators) as search terms: bronchoalveolar lavage AND cytology OR cell AND child. In healthy children, the cell profile includes alveolar macrophages (> 80 percent), lymphocytes (approximately 10 percent), neutrophils (approximately 2 percent) and eosinophils (< 1 percent). The profile varies depending on the disease under study. The number of neutrophils is greater in wheezing children, especially in non-atopic children, as well as in those with pulmonary infectious and inflammatory profiles, including cystic fibrosis and interstitial lung disease. Eosinophil counts are elevated in children/adolescents with asthma and can reach high levels in those with allergic bronchopulmonary aspergillosis or eosinophilic syndromes. In a heterogenous group of diseases, the number of lymphocytes can increase. Evaluation of the BAL fluid cell profile, when used in conjunction with clinical and imaging findings, has proven to be an essential tool in the investigation of various lung diseases. Less invasive than transbronchial and open lung biopsies, BAL has great clinical value. Further studies adopting standard international protocols should be carried out. Such studies should involve various age groups and settings in order to obtain reference values for BAL fluid cell profiles, which are necessary for a more accurate interpretation of findings in children and adolescents with lung diseases.
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Adolescente , Niño , Humanos , Líquido del Lavado Bronquioalveolar/citología , Enfermedades Pulmonares/diagnóstico , Estudios de Casos y Controles , Citodiagnóstico/normas , Enfermedades Pulmonares/clasificaciónRESUMEN
This manuscript reviewed the literature on infection by Mycoplasma pneumoniae with emphasis on etiological aspects of childhood community-acquired pneumonias. Bibliographical research was carried out from Pubmed Medline, MDConsult, HighWire, LILACS, and direct research over the past 10 years with the following keywords: Mycoplasma pneumoniae, pneumonia, and childhood. Fifty-four articles were selected. Mycoplasma pneumoniae has a high incidence in childhood. Clinical presentation includes respiratory and extrarespiratory symptoms. Mycoplasma pneumoniae lung infection can be confused with viral or bacterial pneumonia and is unresponsive to beta-lactams. In addition, co-infections have been reported. Mycoplasma pneumoniae infection occurs in all age groups, being less frequent and more severe in children under the age of five. Its incidence as a causal agent is high. Mycoplasma pneumoniae infections constitute 20 percent-40 percent of all community-acquired pneumonias; the severity is highly variable, and this condition may lead to severe sequelae. Mycoplasma pneumoniae frequency is underestimated in clinical practice because of the lack of specific features and a diagnosis that needs serology or PCR. Effective management of M. pneumoniae infections can usually be achieved with macrolides. In Brazil, epidemiological studies are needed in order to assess the incidence of this bacterium.
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Adolescente , Niño , Preescolar , Femenino , Humanos , Masculino , Asma/etiología , Asma/microbiología , Mycoplasma pneumoniae/patogenicidad , Neumonía por Mycoplasma/complicaciones , Infecciones Comunitarias Adquiridas/microbiología , Encuestas Epidemiológicas , Neumonía por Mycoplasma/microbiología , Factores de Riesgo , Índice de Severidad de la EnfermedadRESUMEN
OBJETIVO: Rever a literatura sobre tratamento da doença do refluxo gastroesofágico (DRGE) com ênfase nos aspectos farmacológicos. Identificar particularidades do tratamento farmacológico nas manifestações esofágicas e extra-esofágicas da doença. FONTES DE DADOS: Busca eletrônica na base de dados PubMed/MEDLINE e Cochrane Collaboration. Procurou-se identificar estudos controlados e randomizados publicados a partir de 2000, bem como revisões que representassem consensos e diretrizes publicados nos últimos 10 anos. SíNTESE DOS DADOS: Nenhuma das drogas atualmente usadas no tratamento da DRGE altera comprovadamente o mecanismo principal da doença, ou seja, os relaxamentos transitórios do esfíncter esofágico inferior. O tratamento farmacológico da DRGE com sintomas ou com lesões esofágicas é baseado na inibição da secreção ácida, em particular pelos inibidores da bomba de prótons (IBP). Nas situações em que a hiper-reatividade das vias aéreas inferiores coexiste com sintomas esofágicos da DRGE, a inibição da secreção ácida deve trazer benefícios na condução da doença respiratória se houver uma relação causal; contudo, essa situação não é comum. Quando não coexistem sintomas esofágicos, a pHmetria esofágica de 24 h deve ser realizada previamente ao tratamento farmacológico da DRGE. A melhora dos sintomas respiratórios pode ser tardia em relação aos sintomas esofágicos. A DRGE freqüentemente recorre, e o tratamento farmacológico deve ser repetido ou mantido indefinidamente, conforme a apresentação clínica da doença. CONCLUSÃO: As condutas propostas para o tratamento farmacológico da DRGE na criança são oriundas principalmente de estudos de séries de casos ou de estudos em adultos. Existem poucos estudos controlados e randomizados em crianças. A realização de um número maior desses estudos poderá reafirmar ou introduzir novos aspectos nas condutas propostas.
OBJECTIVE: To review the literature on the treatment of gastroesophageal reflux disease (GERD) with emphasis on pharmacological aspects. To identify particularities of pharmacological treatment of esophageal and extraesophageal manifestations of the disease. SOURCES: Electronic search of the PubMed/MEDLINE and Cochrane Collaboration databases. Controlled and randomized studies published since 2000 and reviews representing consensus positions and directives published within the last 10 years were identified. SUMMARY OF THE FINDINGS: The drugs currently available for the treatment of GERD do not act in the primary mechanism of the disease, i.e., transitory relaxation of the lower esophageal sphincter. Pharmacological treatment of GERD with symptoms or with esophageal injury is based on the suppression of acid secretion, particularly with proton pump inhibitors. When the hyperreactivity of the lower airways coexists with esophageal GERD symptoms, suppression of acid secretions should be of benefit in managing the respiratory disease in the presence of a causal relationship; however, this is not usual. When esophageal symptoms are not present, esophageal 24-hour pH study should be carried out prior to starting pharmacological treatment for GERD. Improvement of respiratory symptoms may be delayed with relation to esophageal symptoms. It is common for GERD to recur and pharmacological treatment should be repeated or continued indefinitely, depending on clinical presentation of the disease. CONCLUSIONS: The strategies that have been proposed for the pharmacological treatment of GERD in children are primarily based on studies of case series or on studies with adults. There have been very few controlled and randomized studies in children. Undertaking a greater number of these studies might reinforce existing aspects or establish new aspects of management.