RESUMEN
BACKGROUND: STING-associated vasculopathy with onset in infancy (SAVI) is a type 1 interferonopathy manifesting as a pulmonary and vascular syndrome resulting from gain-of-function mutations in TMEM173, the gene encoding STING. Familial reports in the literature are sparse. CASE PRESENTATION: We report a case series of SAVI in a three generation kindred, with a phenotype of interstitial lung disease (ILD) and rheumatoid factor positive polyarticular juvenile idiopathic arthritis (JIA). Current and historical medical records were reviewed for clinical and laboratory information. Whole blood from cases 1 and 2, plus stored appendicectomy tissue from case 3, underwent DNA sequencing of the TMEM173 gene. Peripheral blood RNA was obtained from cases 1 and 2 for functional assessment of the TMEM173 mutation. DNA sequencing identified the same heterozygous TMEM173 mutation (c.463G > A; p.Val155Met) in all three cases, consistent with a diagnosis of the autosomal dominant condition SAVI. Functional assessment of this mutation identified a prominent interferon signature which was confirmed on repeat testing. CONCLUSIONS: SAVI presented in this family as ILD with early onset juvenile rheumatoid arthritis. This condition should be considered in all rheumatoid arthritis patients with early-onset ILD and in all JIA patients with ILD.
Asunto(s)
Artritis Juvenil/fisiopatología , Enfermedades Autoinflamatorias Hereditarias/fisiopatología , Enfermedades Pulmonares Intersticiales/fisiopatología , Proteínas de la Membrana/genética , Enfermedades Vasculares/fisiopatología , Adolescente , Artritis Juvenil/tratamiento farmacológico , Artritis Juvenil/inmunología , Azetidinas/uso terapéutico , Familia , Femenino , Glucocorticoides/uso terapéutico , Enfermedades Autoinflamatorias Hereditarias/tratamiento farmacológico , Enfermedades Autoinflamatorias Hereditarias/genética , Enfermedades Autoinflamatorias Hereditarias/inmunología , Heterocigoto , Humanos , Inmunoglobulinas Intravenosas/uso terapéutico , Factores Inmunológicos/uso terapéutico , Lactante , Recién Nacido , Interferón Tipo I/inmunología , Inhibidores de las Cinasas Janus/uso terapéutico , Enfermedades Pulmonares Intersticiales/tratamiento farmacológico , Enfermedades Pulmonares Intersticiales/inmunología , Mutación , Fenotipo , Purinas/uso terapéutico , Pirazoles/uso terapéutico , Sulfonamidas/uso terapéutico , Síndrome , Enfermedades Vasculares/tratamiento farmacológico , Enfermedades Vasculares/genética , Enfermedades Vasculares/inmunologíaRESUMEN
Heated humidified high-flow nasal cannula therapy (HHHFNC) was originally described as a mode of respiratory support in premature neonates and is now increasingly used in the management of acute respiratory failure in older infants and children. Heating and humidification of gas mixtures allow comfortable delivery of flow rates that match or exceed the patient's inspiratory flow rate. Emerging evidence from observational studies suggests that the use of HHHFNC therapy may be associated with reduced work of breathing, improved ventilation efficiency and a decreased need for intubation in children with respiratory insufficiency. There are several proposed mechanisms of action, and the potential for provision of unpredictable positive distending pressure has caused concern. Randomised controlled trial evidence comparing clinical outcomes with those achieved using other forms of respiratory support is, however, awaited. We review the proposed mechanisms of actions, indications, advantages and complications of HHHFNC therapy in children and describe our approach to its use in the paediatric ward environment.
Asunto(s)
Presión de las Vías Aéreas Positiva Contínua/métodos , Ventilación no Invasiva/métodos , Terapia por Inhalación de Oxígeno/métodos , Síndrome de Dificultad Respiratoria del Recién Nacido/terapia , Niño , Calor , Humanos , Lactante , Recién Nacido , Unidades de Cuidado Intensivo NeonatalRESUMEN
We describe a three generation family in whom multiple individuals are variably affected due to a PHOX2B non-polyalanine repeat mutation. This family demonstrates extreme phenotypic variability and autosomal dominant transmission over three generations not previously reported in the wider literature. Novel findings also inclue a history of recurrent second trimester miscarriage. Pediatr Pulmonol. 2014; 49:E140-E143. © 2014 Wiley Periodicals, Inc.
Asunto(s)
Proteínas de Homeodominio/genética , Hipoventilación/congénito , Mutación , Apnea Central del Sueño/genética , Factores de Transcripción/genética , Aborto Habitual/genética , Femenino , Humanos , Hipoventilación/genética , Lactante , Masculino , Linaje , EmbarazoRESUMEN
BACKGROUND: Mannose-binding lectin (MBL) deficiency has been associated with infections of the respiratory tract and with increased disease severity in cystic fibrosis (CF). The mechanism is uncertain, and could relate either to systemic or local effects. The aim of this study was to determine, in a large cohort of children, whether MBL is present on the airway surface in health or disease. METHODS: Bronchoalveolar lavage (BAL) fluid from children with and without respiratory infection (some with underlying disease) was analysed for MBL and neutrophil elastase (NE). Levels were compared between groups, and correlations were examined with local and systemic inflammatory markers, infective organisms and load. RESULTS: 85 children were recruited to the study. MBL was absent in the lavage of all 7 children without lung infection but present in 62% (8/13) of those with acute pneumonia/pneumonitis, 23% (5/22) with recurrent respiratory tract infections, 17% (1/6) with primary ciliary dyskinesia and 8% (3/37) with CF (p<0.01). Children with acute pneumonia/pneumonitis had significantly higher levels than those in the other groups. There was no relationship with organisms cultured or systemic markers of inflammation, although in the group with detectable MBL in the BAL fluid, the levels correlated positively with levels of NE. CONCLUSIONS: MBL is undetectable in the non-infected airway but is present in a significant number of samples from children with lung infection. The levels found in the BAL fluid could be physiologically active and the protein may therefore be playing a role in host defence.
Asunto(s)
Bronquios/química , Enfermedades Bronquiales/metabolismo , Líquido del Lavado Bronquioalveolar/química , Lectina de Unión a Manosa/metabolismo , Infecciones del Sistema Respiratorio/metabolismo , Adolescente , Bacterias/aislamiento & purificación , Enfermedades Bronquiales/microbiología , Líquido del Lavado Bronquioalveolar/microbiología , Niño , Preescolar , Estudios de Cohortes , Ensayo de Inmunoadsorción Enzimática , Femenino , Genotipo , Haplotipos , Humanos , Lactante , Elastasa de Leucocito/metabolismo , Masculino , Inhibidores de Proteasas/farmacología , Recurrencia , Infecciones del Sistema Respiratorio/microbiología , Virus/aislamiento & purificaciónRESUMEN
Despite the fact that infants spend more time asleep than awake, an understanding of the importance and effects of sleep on the pathophysiology of illness in infancy is a relatively recent development, and is commonly overlooked in paediatric training. In this review we describe some of the characteristics of sleep in infancy, with particular reference to normal developmental physiology and its relevance to the signs, symptoms and pathophysiology of illness in this age group.
Asunto(s)
Sueño/fisiología , Regulación de la Temperatura Corporal/fisiología , Encéfalo/crecimiento & desarrollo , Ritmo Circadiano/fisiología , Sistema Endocrino/fisiología , Humanos , Lactante , RespiraciónRESUMEN
There is little found in the published literature regarding the use of endobronchial biopsy (EBB) in children with cystic fibrosis (CF). One concern over the use of the technique may relate to safety, in particular increased risk of bleeding from a hypertrophied bronchial circulation. The aim of this retrospective study was to compare the safety of EBB in children with CF and those with other conditions, the most frequent of which included primary ciliary dyskinesia and recurrent lower respiratory tract infections. Case notes of all children undergoing EBB in our institution between February 2003 and May 2004 were reviewed. EBB was performed during 45 bronchoscopies in 42 CF patients (19 males, group mean age 7.13 +/- 4.48 years) and in 39 controls (20 males, group mean age 6.59 +/- 4.48 years). There were no significant differences between disease groups in the number, type, or severity of complications occurring during or in the first 12 hr after the procedure. We conclude that EBB performed as part of fibreoptic bronchoscopy (FOB) under general anaesthesia can be performed safely in children with CF, when both bronchoscopist and anaesthetist are suitably experienced. Studies of such samples would allow us to determine the early pathological changes in the CF airway and possibly find new treatments to prevent the progression to bronchiectasis and end stage airway destruction.
Asunto(s)
Biopsia/métodos , Bronquios/patología , Broncoscopía , Fibrosis Quística/patología , Seguridad , Anestesia General , Estudios de Casos y Controles , Niño , Femenino , Tecnología de Fibra Óptica , Humanos , Masculino , Estudios RetrospectivosRESUMEN
AIMS: To gather data on the clinical presentation of parapneumonic effusion and empyema and to examine the effect of different management strategies on short term outcomes. METHODS: Retrospective case note review of 48 children admitted to a tertiary unit between January 1998 and March 2001. Effusions were classified into three stages dependent on ultrasound findings. RESULTS: The stage of effusion was not associated with duration of previous symptoms or length of previous admission. An interventional procedure was performed on median day 2 of admission in 46 children: eight (17%) had an intercostal drain alone, 14 (29%) had an intercostal drain followed by intrapleural fibrinolytic therapy, and 24 (50%) had a thoracotomy. Three children who had an initial intercostal drain alone returned to theatre for thoracotomy, and two children who had intrapleural fibrinolysis returned for thoracotomy. Median length of stay (interquartile range) for each initial procedure was 15 days (6-20) for intercostal drain alone, 8 days (6-12) for fibrinolytic therapy, and 6.5 days (5-9) for thoracotomy. Stay for intercostal drain alone was significantly longer than for thoracotomy. CONCLUSION: Early surgical management of empyema is associated with a favourable outcome.
Asunto(s)
Empiema Pleural/cirugía , Derrame Pleural/cirugía , Adolescente , Tubos Torácicos , Niño , Preescolar , Empiema Pleural/tratamiento farmacológico , Empiema Pleural/microbiología , Femenino , Humanos , Lactante , Recién Nacido , Tiempo de Internación , Masculino , Derrame Pleural/tratamiento farmacológico , Derrame Pleural/microbiología , Estudios Retrospectivos , Toracotomía , Terapia Trombolítica , Resultado del TratamientoRESUMEN
Children with acute asthma account for a significant proportion of paediatric hospital admissions, and clear guidelines exist for their care. The aim of this study was to determine their management in the UK. Over 1 year (February 1995 to January 1996), children aged 1-14 yrs admitted with acute asthma were studied in both teaching and district general hospitals. An admission pro forma was used to collect data prospectively, with a computer-based information management system for the input of admissions in each centre. Ten centres collected data prospectively, with 1,578 admissions involving 1,352 children (median age 3.6 yrs). Sixty two per cent of children were <5 yrs of age. Sixty three per cent of admissions had initial arterial oxygen saturation (Sa,O2) recorded, and, in those older than 5 yrs, 36% had their initial peak expiratory flow rate recorded. Systemic steroids were given to 78%. An initial Sa,O2 of <92% was associated with a longer stay in hospital, and also with intravenous treatment. Preventative treatment increased from 42% on admission to 53% on discharge. The rates of documented education were low. This is the largest UK study following publication of national guidelines and shows that there is still room for improvement in the management of children admitted with acute asthma.