Seguimiento de niños con diagnóstico de asma grave antes y durante la pandemia por COVID-19 / Follow-up of children diagnosed with severe asthma before and during the COVID-19 pandemic

En la pandemia por COVID-19 se exploraron estrategias de atención para garantizar el seguimiento de niños con asma grave. Estudio prospectivo, observacional, comparativo. Se incluyeron pacientes del programa de asma grave de un hospital pediátrico de tercer nivel (n 74). Se evaluó el grado de control, exacerbaciones y hospitalizaciones durante un período presencial (PP), marzo 2019-2020, y uno virtual (PV), abril 2020-2021. En el PP, se incluyeron 74 pacientes vs. 68 (92 %) del PV. En el PP, el 68 % (46) de los pacientes presentaron exacerbaciones vs. el 46 % (31) de los pacientes en el PV (p 0,003). En el PP, se registraron 135 exacerbaciones totales vs. 79 en el PV (p 0,001); hubo una reducción del 41 %. En el PP, el 47 % (32) de los pacientes tuvieron exacerbaciones graves vs. el 32 % (22) de los pacientes en el PV (p 0,048). Hubo 91 exacerbaciones graves en el PP vs. 49 en el PV (p 0,029), reducción del 46 %. No hubo diferencias en las hospitalizaciones (PP 10, PV 6; p 0,9). La telemedicina fue efectiva para el seguimiento de pacientes con asma grave

During the COVID-19 pandemic, health care strategies were explored to ensure the follow-up of children with severe asthma. This was a prospective, observational, and comparative study. Patients in the severe asthma program of a tertiary care children's hospital were included (n: 74). The extent of control, exacerbations, and hospitalizations during an in-person period (IPP) (March 2019­2020) and an online period (OP) (April 2020­2021) was assessed. A total of 74 patients were enrolled in the IPP compared to 68 (92%) in the OP. During the IPP, 68% (46) of patients had exacerbations versus 46% (31) during the OP (p = 0.003). During the IPP, 135 total exacerbations were recorded compared to 79 during the OP (p = 0.001); this accounted for a 41% reduction. During the IPP, 47% (32) of patients had severe exacerbations versus 32% (22) during the OP (p = 0.048). A total of 91 severe exacerbations were recorded during the IPP compared to 49 during the OP (p = 0.029); the reduction was 46%. No differences were observed in terms of hospitalization (IPP: 10, OP: 6; p = 0,9). Telemedicine was effective for the follow-up of patients with severe asthma.

Follow-up of children diagnosed with severe asthma before and during the COVID-19 pandemic. / Seguimiento de niños con diagnóstico de asma grave antes y durante la pandemia por COVID-19.

During the COVID-19 pandemic, health care strategies were explored to ensure the follow-up of children with severe asthma. This was a prospective, observational, and comparative study. Patients in the severe asthma program of a tertiary care children's hospital were included (n: 74). The extent of control, exacerbations, and hospitalizations during an in-person period (IPP) (March 2019-2020) and an online period (OP) (April 2020-2021) was assessed. A total of 74 patients were enrolled in the IPP compared to 68 (92%) in the OP. During the IPP, 68% (46) of patients had exacerbations versus 46% (31) during the OP (p = 0.003). During the IPP, 135 total exacerbations were recorded compared to 79 during the OP (p = 0.001); this accounted for a 41% reduction. During the IPP, 47% (32) of patients had severe exacerbations versus 32% (22) during the OP (p = 0.048). A total of 91 severe exacerbations were recorded during the IPP compared to 49 during the OP (p = 0.029); the reduction was 46%. No differences were observed in terms of hospitalization (IPP: 10, OP: 6; p = 0,9). Telemedicine was effective for the follow-up of patients with severe asthma.

En la pandemia por COVID-19 se exploraron estrategias de atención para garantizar el seguimiento de niños con asma grave. Estudio prospectivo, observacional, comparativo. Se incluyeron pacientes del programa de asma grave de un hospital pediátrico de tercer nivel (n 74). Se evaluó el grado de control, exacerbaciones y hospitalizaciones durante un período presencial (PP), marzo 2019-2020, y uno virtual (PV), abril 2020-2021. En el PP, se incluyeron 74 pacientes vs. 68 (92 %) del PV. En el PP, el 68 % (46) de los pacientes presentaron exacerbaciones vs. el 46 % (31) de los pacientes en el PV (p 0,003). En el PP, se registraron 135 exacerbaciones totales vs. 79 en el PV (p 0,001); hubo una reducción del 41 %. En el PP, el 47 % (32) de los pacientes tuvieron exacerbaciones graves vs. el 32 % (22) de los pacientes en el PV (p 0,048). Hubo 91 exacerbaciones graves en el PP vs. 49 en el PV (p 0,029), reducción del 46 %. No hubo diferencias en las hospitalizaciones (PP 10, PV 6; p 0,9). La telemedicina fue efectiva para el seguimiento de pacientes con asma grave.

Hemoptisis secundaria a tuberculosis pulmonar complicada con pseudoaneurisma de Rasmussen. Reporte de un caso en pediatría. / Hemoptysis in Pulmonary Tuberculosis Complicated by Rasmussen's Pseudoaneurysm. A Pediatric Case Report.

Presentamos el caso de un niño de 12 años que consultó por hemoptisis, sin otros sín- tomas asociados. Se realizó radiografía de tórax (patológica), laboratorio con aumen- to moderado de reactantes de fase aguda, PPD (negativa), esputos x 3 con bacilosco- pias negativas y tomografía de tórax con contraste i.v. que mostró imágenes de árbol en brote en todos los lóbulos y una imagen de dilatación vascular de una rama de la ar- teria pulmonar en lóbulo superior izquierdo. Se plantearon diagnósticos diferenciales: malformación vascular primaria o lesión secundaria a infección. La angiografía digital permitió confirmar el pseudoaneurisma y embolizarlo. Luego de 17 días, 2/3 cultivos de esputo fueron positivos para Mycobacterium tuberculosis. El niño realizó tratamiento antituberculoso con drogas de primera línea con evolución clínica favorable. Este caso resalta la importancia de considerar el pseudoaneurisma de Rasmussen en- tre las posibles complicaciones de un paciente con tuberculosis y hemoptisis recurren- te o masiva.

We present the case of a 12-year-old boy admitted to the hospital due to hemoptysis without other symptoms. We performed a Thorax X-Ray (pathological), laboratory with elevated acute phase reactants, TST (negative), sputum x 3 with negative smear and computed tomography angiography showing a tree-in-bud pattern in all lobes, and di-latation of a brunch of the pulmonary artery in the upper left lobe. We considered pri-mary vascular anomaly or lesion due to infection as a differential diagnosis. The patient underwent digital angiography and therapeutic embolization of this pseudoaneurysm. After seventeen days, 2/3 of the sputum cultures were positive for Mycobacterium tu-berculosis. The patient received standard anti-TB therapy with favorable evolution. This case highlights the importance of considering complications such as Rasmussen's pseudoaneurysm in patients with pulmonary tuberculosis and recurrent or massive hemoptysis.

Pulmonary surfactant metabolism dysfunction: A pediatric clinical case report. / Disfunciones del metabolismo del surfactante pulmonar: caso clínico pediátrico.

Interstitial lung diseases are rare in pediatrics. They include dysfunctions in the metabolism of pulmonary surfactant, an amphipathic molecule that reduces surface tension and prevents alveolar collapse. Here we describe the case of a 6-month-old infant controlled for low weight, who presented with acute respiratory distress and cyanosis; his chest X-ray showed interstitial infiltrate, pneumomediastinum, and bilateral pneumothorax. During history-taking, it was noted that his mother had a history of hospitalization at 1 year old with unknown diagnosis, requiring prolonged oxygen therapy; she now shows signs of chronic hypoxia. The patient was hospitalized and required oxygen therapy. Ancillary tests were done to look for the etiology of the condition, with no positive results. A chest computed tomography showed groundglass opacities, thickening of the septal interstitium, and areas of air trapping; based on the results of a lung biopsy and a genetic study, pulmonary surfactant metabolism dysfunction was diagnosed.

Las enfermedades pulmonares intersticiales son patologías poco frecuentes en pediatría. Dentro de ellas, se incluyen las disfunciones del metabolismo del surfactante pulmonar, molécula anfipática cuya función es disminuir la tensión superficial y evitar el colapso alveolar. Se presenta el caso de un lactante de 6 meses, en seguimiento por bajo peso, que presentó dificultad respiratoria aguda y cianosis; la radiografía de tórax evidenció infiltrado intersticial, neumomediastino neumotórax bilateral. Al interrogatorio, surgió antecedente materno de internación al año de vida, con requerimiento de oxigenoterapia prolongada y diagnóstico desconocido; presenta signos de hipoxia crónica. El paciente cursó internación con requerimiento de oxigenoterapia. Se realizaron estudios complementarios en búsqueda de etiología, sin resultados positivos. La tomografía de tórax evidenció opacidades en vidrio esmerilado, engrosamiento del intersticio septal y áreas de atrapamiento aéreo; con resultado de biopsia pulmonar y estudio genético se llegó al diagnóstico de disfunción del metabolismo del surfactante pulmonar.

Evolución clínico funcional de pacientes con fibrosis quística tratados con lumacaftor/ivacaftor en un centro pediátrico. Serie de casos / Clinical and functional course of patients with cystic fibrosis treated with lumacaftor/ivacaftor at a children's hospital. A case series

Los moduladores de la proteína reguladora transmembrana de fibrosis quística (CFTR) tratan el defecto de esta proteína. El objetivo es describir la evolución de niños con fibrosis quística tratados con lumacaftor/ivacaftor. Se trata de una serie de 13 pacientes de 6 a 18 años con ≥ 6 meses de tratamiento. Se analizaron el volumen espiratorio forzado en el primer segundo (VEF1), puntaje Z del índice de masa corporal (IMC), antibioticoterapia/año, antes del tratamiento y durante 24 meses posteriores. A los 12 meses (9/13) y 24 meses (5/13), la mediana de cambio del porcentaje del predicho VEF1 (ppVEF1) fue de 0,5 pp [-2-12] y 15 pp [8,7-15,2], y del puntaje Z de IMC de 0,32 puntos [-0,2-0,5] y 1,23 puntos [0,3-1,6]. El primer año (11/13) la mediana de días de uso de antibiótico disminuyó de 57 a 28 (oral) y de 27 a 0 (intravenoso). Dos niños evidenciaron eventos adversos asociados.

Cystic fibrosis transmembrane regulator (CFTR) modulators treat defective CFTR protein. Our objective is to describe the course of children with cystic fibrosis treated with lumacaftor/ivacaftor. This is a case series of 13 patients aged 6 to 18 years with ≥ 6 months of treatment. Forced expiratory volume in the first second (FEV1), body mass index (BMI) Z-score, antibiotic therapy/year, before treatment and for 24 months after treatment were analyzed. At 12 months (9/13) and 24 months (5/13), the median change in the percent predicted FEV1 (ppFEV1) was 0.5 pp (-2­12) and 15 pp (8.7­15.2) and the BMI Z-score was 0.32 points (-0.2­0.5) and 1.23 points (0.3­1.6). In the first year, in 11/13 patients, the median number of days of antibiotic use decreased from 57 to 28 (oral) and from 27 to 0 (intravenous). Two children had associated adverse events.

Neumotórax espontáneo persistente como manifestación primaria de sarcoma sinovial pleuropulmonar primario: a propósito de un caso / Persistent spontaneous pneumothorax as a primary manifestation of primary synovial sarcoma of the lung: a case report

El sarcoma sinovial pleuropulmonar (SSPP) es un tumor primario de pulmón, maligno, infrecuente en pediatría (prevalencia 0,1-0,5 %) que afecta predominantemente a adolescentes y adultos jóvenes. Se ha descrito una sobrevida global cercana al 30 % a los 5 años. Se reporta el caso de un paciente de 12 años de edad, previamente sano, que presentó tos, dolor torácico y disnea de comienzo súbito, como manifestación inicial de neumotórax izquierdo, el que persistió a los 4 días y requirió resección quirúrgica de lesión bullosa pulmonar. Se realizó diagnóstico histológico de sarcoma sinovial pleuropulmonar confirmado por estudio molecular, que evidenció la translocación cromosómica entre el cromosoma X y el 18: t(X;18) (p11.2;q11.2) de la pieza quirúrgica extirpada. Ante pacientes con neumotórax persistente o recidivante, es importante descartar causas secundarias, entre ellas, sarcoma sinovial pleuropulmonar. Su ominoso pronóstico determina la necesidad de arribar a un diagnóstico temprano e implementar un tratamiento agresivo

Pleuropulmonary synovial sarcoma (PPSS) is a primary malignancy of the lung, uncommon in pediatrics (prevalence: 0.1­0.5%) that predominantly affects adolescents and young adults. Overall survival has been reported to be close to 30% at 5 years. Here we report the case of a previously healthy 12-year-old male patient who presented with cough, chest pain, and dyspnea of sudden onset as initial manifestation of left pneumothorax, which persisted after 4 days and required surgical resection of pulmonary bullous lesion. A histological diagnosis of pleuropulmonary synovial sarcoma was made and confirmed by molecular study, which showed chromosomal translocation between chromosomes X and 18: t(X;18) (p11.2;q11.2) in the surgical specimen removed. In patients with persistent or recurrent pneumothorax, it is important to rule out secondary causes, including pleuropulmonary synovial sarcoma. Such poor prognosis determines the need for early diagnosis and aggressive treatment.

Clinical and functional course of patients with cystic fibrosis treated with lumacaftor/ivacaftor at a children's hospital. A case series. / Evolución clínico funcional de pacientes con fibrosis quística tratados con lumacaftor/ivacaftor en un centro pediátrico. Serie de casos.

Cystic fibrosis transmembrane regulator (CFTR) modulators treat defective CFTR protein. Our objective is to describe the course of children with cystic fibrosis treated with lumacaftor/ivacaftor. This is a case series of 13 patients aged 6 to 18 years with ≥ 6 months of treatment. Forced expiratory volume in the first second (FEV1), body mass index (BMI) Z-score, antibiotic therapy/year, before treatment and for 24 months after treatment were analyzed. At 12 months (9/13) and 24 months (5/13), the median change in the percent predicted FEV1 (ppFEV1) was 0.5 pp (-2-12) and 15 pp (8.7-15.2) and the BMI Z-score was 0.32 points (-0.2-0.5) and 1.23 points (0.3-1.6). In the first year, in 11/13 patients, the median number of days of antibiotic use decreased from 57 to 28 (oral) and from 27 to 0 (intravenous). Two children had associated adverse events.

Los moduladores de la proteína reguladora transmembrana de fibrosis quística (CFTR) tratan el defecto de esta proteína. El objetivo es describir la evolución de niños con fibrosis quística tratados con lumacaftor/ivacaftor. Se trata de una serie de 13 pacientes de 6 a 18 años con ≥ 6 meses de tratamiento. Se analizaron el volumen espiratorio forzado en el primer segundo (VEF1), puntaje Z del índice de masa corporal (IMC), antibioticoterapia/año, antes del tratamiento y durante 24 meses posteriores. A los 12 meses (9/13) y 24 meses (5/13), la mediana de cambio del porcentaje del predicho VEF1 (ppVEF1) fue de 0,5 pp [-2-12] y 15 pp [8,7-15,2], y del puntaje Z de IMC de 0,32 puntos [-0,2-0,5] y 1,23 puntos [0,3-1,6]. El primer año (11/13) la mediana de días de uso de antibiótico disminuyó de 57 a 28 (oral) y de 27 a 0 (intravenoso). Dos niños evidenciaron eventos adversos asociados.

Persistent spontaneous pneumothorax as a primary manifestation of primary synovial sarcoma of the lung: a case report. / Neumotórax espontáneo persistente como manifestación primaria de sarcoma sinovial pleuropulmonar primario: a propósito de un caso.

Pleuropulmonary synovial sarcoma (PPSS) is a primary malignancy of the lung, uncommon in pediatrics (prevalence: 0.1-0.5%) that predominantly affects adolescents and young adults. Overall survival has been reported to be close to 30% at 5 years. Here we report the case of a previously healthy 12-year-old male patient who presented with cough, chest pain, and dyspnea of sudden onset as initial manifestation of left pneumothorax, which persisted after 4 days and required surgical resection of pulmonary bullous lesion. A histological diagnosis of pleuropulmonary synovial sarcoma was made and confirmed by molecular study, which showed chromosomal translocation between chromosomes X and 18: t(X;18) (p11.2;q11.2) in the surgical specimen removed. In patients with persistent or recurrent pneumothorax, it is important to rule out secondary causes, including pleuropulmonary synovial sarcoma. Such poor prognosis determines the need for early diagnosis and aggressive treatment.

El sarcoma sinovial pleuropulmonar (SSPP) es un tumor primario de pulmón, maligno, infrecuente en pediatría (prevalencia 0,1-0,5 %) que afecta predominantemente a adolescentes y adultos jóvenes. Se ha descrito una sobrevida global cercana al 30 % a los 5 años. Se reporta el caso de un paciente de 12 años de edad, previamente sano, que presentó tos, dolor torácico y disnea de comienzo súbito, como manifestación inicial de neumotórax izquierdo, el que persistió a los 4 días y requirió resección quirúrgica de lesión bullosa pulmonar. Se realizó diagnóstico histológico de sarcoma sinovial pleuropulmonar confirmado por estudio molecular, que evidenció la translocación cromosómica entre el cromosoma X y el 18: t(X;18) (p11.2;q11.2) de la pieza quirúrgica extirpada. Ante pacientes con neumotórax persistente o recidivante, es importante descartar causas secundarias, entre ellas, sarcoma sinovial pleuropulmonar. Su ominoso pronóstico determina la necesidad de arribar a un diagnóstico temprano e implementar un tratamiento agresivo.

Pulmonary Alveolar Proteinosis and Multiple Infectious Diseases in a Child with Autosomal Recessive Complete IRF8 Deficiency.

BACKGROUND: Autosomal recessive (AR) complete IRF8 deficiency is a rare severe inborn error of immunity underlying an absence of blood myeloid mononuclear cells, intracerebral calcifications, and multiple infections. Only three unrelated patients have been reported. MATERIALS AND METHODS: We studied an Argentinian child with multiple infectious diseases and severe pulmonary alveolar proteinosis (PAP). We performed whole-exome sequencing (WES) and characterized his condition by genetic, immunological, and clinical means. RESULTS: The patient was born and lived in Argentina. He had a history of viral pulmonary diseases, disseminated disease due to bacillus Calmette-Guérin (BCG), PAP, and cerebral calcifications. He died at the age of 10 months from refractory PAP. WES identified two compound heterozygous variants in IRF8: c.55del and p.R111*. In an overexpression system, the p.R111* cDNA was loss-of-expression, whereas the c.55del cDNA yielded a protein with a slightly lower molecular weight than the wild-type protein. The mutagenesis of methionine residues downstream from c.55del revealed a re-initiation of translation. However, both variants were loss-of-function in a luciferase assay, suggesting that the patient had AR complete IRF8 deficiency. The patient had no blood monocytes or dendritic cells, associated with neutrophilia, and normal counts of NK and other lymphoid cell subsets. CONCLUSION: We describe the fourth patient with AR complete IRF8 deficiency. This diagnosis should be considered in children with PAP, which is probably due to the defective development or function of alveolar macrophages.

Clinical characteristics of SARS-CoV-2 infection in children with cystic fibrosis: An international observational study.

BACKGROUND: The presence of co-morbidities, including underlying respiratory problems, has been identified as a risk factor for severe COVID-19 disease. Information on the clinical course of SARS-CoV-2 infection in children with cystic fibrosis (CF) is limited, yet vital to provide accurate advice for children with CF, their families, caregivers and clinical teams. METHODS: Cases of SARS-CoV-2 infection in children with CF aged less than 18 years were collated by the CF Registry Global Harmonization Group across 13 countries between 1 February and 7 August 2020. RESULTS: Data on 105 children were collated and analysed. Median age of cases was ten years (interquartile range 6-15), 54% were male and median percentage predicted forced expiratory volume in one second was 94% (interquartile range 79-104). The majority (71%) of children were managed in the community during their COVID-19 illness. Out of 24 children admitted to hospital, six required supplementary oxygen and two non-invasive ventilation. Around half were prescribed antibiotics, five children received antiviral treatments, four azithromycin and one additional corticosteroids. Children that were hospitalised had lower lung function and reduced body mass index Z-scores. One child died six weeks after testing positive for SARS-CoV-2 following a deterioration that was not attributed to COVID-19 disease. CONCLUSIONS: SARS-CoV-2 infection in children with CF is usually associated with a mild illness in those who do not have pre-existing severe lung disease.

The future of cystic fibrosis care: a global perspective.

The past six decades have seen remarkable improvements in health outcomes for people with cystic fibrosis, which was once a fatal disease of infants and young children. However, although life expectancy for people with cystic fibrosis has increased substantially, the disease continues to limit survival and quality of life, and results in a large burden of care for people with cystic fibrosis and their families. Furthermore, epidemiological studies in the past two decades have shown that cystic fibrosis occurs and is more frequent than was previously thought in populations of non-European descent, and the disease is now recognised in many regions of the world. The Lancet Respiratory Medicine Commission on the future of cystic fibrosis care was established at a time of great change in the clinical care of people with the disease, with a growing population of adult patients, widespread genetic testing supporting the diagnosis of cystic fibrosis, and the development of therapies targeting defects in the cystic fibrosis transmembrane conductance regulator (CFTR), which are likely to affect the natural trajectory of the disease. The aim of the Commission was to bring to the attention of patients, health-care professionals, researchers, funders, service providers, and policy makers the various challenges associated with the changing landscape of cystic fibrosis care and the opportunities available for progress, providing a blueprint for the future of cystic fibrosis care. The discovery of the CFTR gene in the late 1980s triggered a surge of basic research that enhanced understanding of the pathophysiology and the genotype-phenotype relationships of this clinically variable disease. Until recently, available treatments could only control symptoms and restrict the complications of cystic fibrosis, but advances in CFTR modulator therapies to address the basic defect of cystic fibrosis have been remarkable and the field is evolving rapidly. However, CFTR modulators approved for use to date are highly expensive, which has prompted questions about the affordability of new treatments and served to emphasise the considerable gap in health outcomes for patients with cystic fibrosis between high-income countries, and low-income and middle-income countries (LMICs). Advances in clinical care have been multifaceted and include earlier diagnosis through the implementation of newborn screening programmes, formalised airway clearance therapy, and reduced malnutrition through the use of effective pancreatic enzyme replacement and a high-energy, high-protein diet. Centre-based care has become the norm in high-income countries, allowing patients to benefit from the skills of expert members of multidisciplinary teams. Pharmacological interventions to address respiratory manifestations now include drugs that target airway mucus and airway surface liquid hydration, and antimicrobial therapies such as antibiotic eradication treatment in early-stage infections and protocols for maintenance therapy of chronic infections. Despite the recent breakthrough with CFTR modulators for cystic fibrosis, the development of novel mucolytic, anti-inflammatory, and anti-infective therapies is likely to remain important, especially for patients with more advanced stages of lung disease. As the median age of patients with cystic fibrosis increases, with a rapid increase in the population of adults living with the disease, complications of cystic fibrosis are becoming increasingly common. Steps need to be taken to ensure that enough highly qualified professionals are present in cystic fibrosis centres to meet the needs of ageing patients, and new technologies need to be adopted to support communication between patients and health-care providers. In considering the future of cystic fibrosis care, the Commission focused on five key areas, which are discussed in this report: the changing epidemiology of cystic fibrosis (section 1); future challenges of clinical care and its delivery (section 2); the building of cystic fibrosis care globally (section 3); novel therapeutics (section 4); and patient engagement (section 5). In panel 1, we summarise key messages of the Commission. The challenges faced by all stakeholders in building and developing cystic fibrosis care globally are substantial, but many opportunities exist for improved care and health outcomes for patients in countries with established cystic fibrosis care programmes, and in LMICs where integrated multidisciplinary care is not available and resources are lacking at present. A concerted effort is needed to ensure that all patients with cystic fibrosis have access to high-quality health care in the future.

Key factors associated with uncontrolled asthma - the Asthma Control in Latin America Study.

Objective: This study aimed to estimate asthma control at specialist treatment centers in four Latin American countries and assess factors influencing poor asthma control.Methods: Patients aged ≥12 years with an asthma diagnosis and asthma medication prescription, followed at outpatient specialist centers in Argentina, Chile, Colombia, and Mexico, were included. The study received all applicable ethical approvals. The Asthma Control Test (ACT) was used to classify patients as having controlled (ACT 20-25) or uncontrolled (ACT ≤19) asthma. Frequency and statistical tests were used to assess the association between hospital admissions/exacerbations/emergency department (ED) visits and uncontrolled asthma; multivariate logistic regression was used to assess the association of uncontrolled asthma with clinical/demographic variables.Results: A total of 594 patients were included. Overall controlled-asthma prevalence was 43.4% (95% confidence interval [CI]: 39.0, 47.4). Patients with uncontrolled asthma were more likely to be women (adjusted odds ratio [aOR]: 1.85; p = 0.003), non-white (aOR: 2.14; p < 0.001), obese (aOR: 1.71; p = 0.036), to have a low monthly family income (aOR: 1.75; p = 0.004), to have severe asthma (aOR:1.59; p = 0.26), and, compared with patients with controlled asthma, to have a higher likelihood of asthma exacerbations (34.5% vs. 15.9%; p < 0.001), hospital admissions (6.9% vs. 3.1%; p = 0.042), and ED visits (34.5% vs. 15.9%; p < 0.001) due to asthma.Conclusions: Even in specialist ambulatory services, fewer than half of patients were classified as having controlled asthma. The proportion of uncontrolled patients varied according to clinical and demographic variables.

Population pharmacokinetics of amikacin in patients with pediatric cystic fibrosis.

INTRODUCTION: Amikacin is commonly used in patients with pediatric cystic fibrosis (CF) for the treatment of pulmonary exacerbations. Amikacin efficacy is related to maximum plasma concentration/minimum inhibitory concentration (Cmax/MIC) ratio >8. Pharmacokinetic data in patients with pediatric CF are scarce. The aim of this study was to develop a population pharmacokinetic (PopPK) model describing amikacin disposition in patients with pediatric CF. METHODS: CF patients under 18 years of age with pulmonary exacerbation who received amikacin were enrolled. Patients received different amikacin regimens (30 mg-1 kg-1 day-1 every 8, 12, or 24 hours) depending on the patient's status and hospital protocols. Amikacin serum levels were obtained for therapeutic drug monitoring. PopPK model was developed using MONOLIX Suite-2018R1 (Lixoft). RESULTS: A total of 39 patients (114 amikacin concentrations) were included in this study. Population estimates for the elimination rate constant (k) and the volume of distribution (V) were 0.541 hours-1 and 0.451 L/kg, respectively. Between-subject and between-occasion variability were 53% and 16.5% for k and 31% and 22% for V, respectively. Bodyweight was a significant covariate associated with V. Based on simulations, almost 70% of the patients receiving 30 mg-1 kg-1 day-1 every 24 hours would achieve a Cmax/MIC ratio >8 which is an appropriate therapeutic goal while no patient in the other two groups (Q8 and Q12) would achieve that objective. CONCLUSIONS: The regimen of 30 mg-1 kg-1 day-1 every 24 hours more adequately fulfilled the therapeutic target for amikacin. Although all our patients had good clinical results and a good adverse-events profile, further studies are necessary to redefine the optimal treatment strategy.

Impacto clínico del tratamiento con omalizumab en niños con asma grave: Reporte de una experiencia local / Clinical impact of omalizumab treatment in children with severe asthma: Report of a local experience

El anticuerpo monoclonal anti-IgE omalizumab está indicado para tratamiento del asma grave. Estudio longitudinal (pre-posintervención), observacional y analítico con el objetivo de evaluar la evolución clínica y funcional de pacientes con asma grave no controlada, 16 semanas antes y después del tratamiento. En los 17 casos, se controló el asma (p= 0,00001). Se redujeron en un 48,5 % las exacerbaciones (p= 0,009) y en un 100 % las crisis graves (p= 0,001). Dieciséis pacientes (el 94 %) tuvieron exacerbaciones pretratamiento y 10 (el 59 %), luego del omalizumab (p= 0,005). No hubo hospitalizaciones (p= 0,007). Se redujo en un 20 % la dosis de corticoides inhalados (0,002) y el número de casos con corticoides orales continuos (p= 0,01); disminuyó el uso de salbutamol (p= 0,001) y de corticoides orales (p= 0,003). No se modificó la función pulmonar. Dos casos presentaron reacciones adversas leves. El omalizumab permitió un adecuado control de la enfermedad en pacientes con asma grave.

Omalizumab, an anti-IgE monoclonal antibody, is indicated for the treatment of severe asthma. A longitudinal (pre-/post-intervention), observational, analytical study was conducted to assess the clinical and functional course of patients with uncontrolled severe asthma, 16 weeks before and after treatment. Asthma was controlled in 17 cases (p = 0.00001). Exacerbations were reduced by 48.5 % (p = 0.009) and severe crises, by 100 % (p = 0.001). Before omalizumab treatment, 16 patients (94 %) had exacerbations, whereas 10 (59 %) had them after treatment (p = 0.005). None of the patients was hospitalized (p = 0.007). The dose of inhaled corticosteroids was reduced by 20 % (0.002); the number of patients using continuous oral corticosteroids (p = 0.01), salbutamol (p = 0.001), and oral corticosteroids (p=0.003) also decreased. Pulmonary function was not affected. Two patients had mild adverse reactions. Omalizumab achieved an adequate asthma control in patients with severe asthma.

Neumonía bullosa secundaria a Elizabethkingia meningoseptica, su evolución clínica y radiológica / Bullous pneumonia secondary to Elizabethkingia meningoseptica, its clinical and radiological evolution

Elizabethkingia meningoseptica es un patógeno oportunista, con una elevada mortalidad y una incidencia en aumento en las terapias intensivas. Se presenta a una paciente de 4 años con antecedente de atresia de vías biliares y trasplante hepático a los 11 meses de vida, que se internó por infección respiratoria aguda baja con hipoxemia. Durante la internación, sufrió un empeoramiento clínico con requerimiento de asistencia respiratoria mecánica. Por fiebre e hipoxemia persistente, se realizó un minilavado broncoalveolar, con cultivo positivo para Elizabethkingia meningoseptica. Recibió vancomicina, trimetoprima/sulfametoxazol y ciprofloxacina durante 14 días, con buena respuesta. Una tomografía de tórax evidenció la presencia de hipoperfusión en mosaico, imágenes quísticas y bronquiectasias bilaterales. Durante los siguientes 2 años, presentó una buena evolución clínica, con escasas intercurrencias respiratorias, síntomas intercrisis aislados y buena tolerancia al ejercicio. En las imágenes de control, se evidenció la resolución de la mayoría de las lesiones iniciales a los 20 meses de su seguimiento.

Elizabethkingia meningoseptica is an opportunistic pathogen with a high mortality and an increasing incidence in the intensive care units. We present a 4-year-old patient with a history of atresia of the biliary tract and a liver transplant at 11 months of age, who was admitted for acute respiratory infection with hypoxemia. During the hospitalization, she required mechanical ventilation. Due to persistent fever and hypoxemia, mini bronchoalveolar lavage was performed with a positive culture for Elizabethkingia meningoseptica. She received vancomycin, trimethoprim/sulfamethoxazole and ciprofloxacin for 14 days with a good response. A chest tomography showed the presence of mosaic hypoperfusion, cystic images, and bilateral bronchiectasis. During the following 2 years, she presented good clinical progress, with scarce respiratory infections, isolated symptoms and good tolerance to exercise. The resolution of the majority of the initial lesions was evidenced at 20 months of follow-up.

Clinical impact of omalizumab treatment in children with severe asthma: Report of a local experience. / Impacto clínico del tratamiento con omalizumab en niños con asma grave: Reporte de una experiencia local.

Omalizumab, an anti-IgE monoclonal antibody, is indicated for the treatment of severe asthma. A longitudinal (pre-/post-intervention), observational, analytical study was conducted to assess the clinical and functional course of patients with uncontrolled severe asthma, 16 weeks before and after treatment. Asthma was controlled in 17 cases (p = 0.00001). Exacerbations were reduced by 48.5 % (p = 0.009) and severe crises, by 100 % (p = 0.001). Before omalizumab treatment, 16 patients (94 %) had exacerbations, whereas 10 (59 %) had them after treatment (p = 0.005). None of the patients was hospitalized (p = 0.007). The dose of inhaled corticosteroids was reduced by 20 % (0.002); the number of patients using continuous oral corticosteroids (p = 0.01), salbutamol (p = 0.001), and oral corticosteroids (p=0.003) also decreased. Pulmonary function was not affected. Two patients had mild adverse reactions. Omalizumab achieved an adequate asthma control in patients with severe asthma.

El anticuerpo monoclonal anti-IgE omalizumab está indicado para tratamiento del asma grave. Estudio longitudinal (pre-posintervención), observacional y analítico con el objetivo de evaluar la evolución clínica y funcional de pacientes con asma grave no controlada, 16 semanas antes y después del tratamiento. En los 17 casos, se controló el asma (p= 0,00001). Se redujeron en un 48,5 % las exacerbaciones (p= 0,009) y en un 100 % las crisis graves (p= 0,001). Dieciséis pacientes (el 94 %) tuvieron exacerbaciones pretratamiento y 10 (el 59 %), luego del omalizumab (p= 0,005). No hubo hospitalizaciones (p= 0,007). Se redujo en un 20 % la dosis de corticoides inhalados (0,002) y el número de casos con corticoides orales continuos (p= 0,01); disminuyó el uso de salbutamol (p= 0,001) y de corticoides orales (p= 0,003). No se modificó la función pulmonar. Dos casos presentaron reacciones adversas leves. El omalizumab permitió un adecuado control de la enfermedad en pacientes con asma grave.

[Bullous pneumonia secondary to Elizabethkingia meningoseptica, its clinical and radiological evolution]. / Neumonía bullosa secundaria aElizabethkingia meningoseptica, su evolución clínica y radiológica.

Elizabethkingia meningoseptica is an opportunistic pathogen with a high mortality and an increasing incidence in the intensive care units. We present a 4-year-old patient with a history of atresia of the biliary tract and a liver transplant at 11 months of age, who was admitted for acute respiratory infection with hypoxemia. During the hospitalization, she required mechanical ventilation. Due to persistent fever and hypoxemia, mini bronchoalveolar lavage was performed with a positive culture for Elizabethkingia meningoseptica. She received vancomycin, trimethoprim/sulfamethoxazole and ciprofloxacin for 14 days with a good response. A chest tomography showed the presence of mosaic hypoperfusion, cystic images, and bilateral bronchiectasis. During the following 2 years, she presented good clinical progress, with scarce respiratory infections, isolated symptoms and good tolerance to exercise. The resolution of the majority of the initial lesions was evidenced at 20 months of follow-up.

Elizabethkingia meningoseptica es un patógeno oportunista, con una elevada mortalidad y una incidencia en aumento en las terapias intensivas. Se presenta a una paciente de 4 años con antecedente de atresia de vías biliares y trasplante hepático a los 11 meses de vida, que se internó por infección respiratoria aguda baja con hipoxemia. Durante la internación, sufrió un empeoramiento clínico con requerimiento de asistencia respiratoria mecánica. Por fiebre e hipoxemia persistente, se realizó un minilavado broncoalveolar, con cultivo positivo para Elizabethkingia meningoseptica. Recibió vancomicina, trimetoprima/sulfametoxazol y ciprofloxacina durante 14 días, con buena respuesta. Una tomografía de tórax evidenció la presencia de hipoperfusión en mosaico, imágenes quísticas y bronquiectasias bilaterales. Durante los siguientes 2 años, presentó una buena evolución clínica, con escasas intercurrencias respiratorias, síntomas intercrisis aislados y buena tolerancia al ejercicio. En las imágenes de control, se evidenció la resolución de la mayoría de las lesiones iniciales a los 20 meses de su seguimiento.

Disseminated visceral Kaposi´s sarcoma in a pediatric bilateral lung transplant recipient.

Cancer is a major adverse outcome of solid organ transplantation, and risks are especially high for malignancies caused by viral infections. HHV-8 is the etiologic agent of Kaposi´s sarcoma (KS). We report a case of visceral KS occurring in a 15-year-old patient after lung transplantation. The evolution was dramatically fast and interestingly, KS lesions were diffusely observed, but not in the skin. The autopsy showed the presence of numerous tumoral lesions in many organs. Microscopically, they all had very similar features, regardless of the organ affected. KS presented without cutaneous involvement. The girl was not tested for HHV-8 prior to transplantation as it was not part of our protocol. The donor was negative. The aim of the report is to alert other teams, especially those working in pediatrics, about this rare but potential complication in the setting of solid organ transplantation.

Asma grave en pediatría: resultados de la implementación de un protocolo especial de atención / Severe asthma in pediatrics: Outcomes of the implementation of a special health care protocol

Introducción. El asma grave representa 5-7% del total de asmáticos. La OMS propuso un protocolo de seguimiento para categorizarlos como asma grave resistente al tratamiento (AGRT) o asma grave de difícil control (AGDC). Objetivo. Analizar las características clínicas, funcionales y terapéuticas de pacientes con AGRT o AGDC. Métodos. Estudio transversal, observacional y analítico para evaluar el diagnóstico, grado de control (clínico y funcional), comorbilidades, adherencia al tratamiento, técnica inhalatoria y factores ambientales en pacientes con asma grave. Resultados. Se incluyeron 69 pacientes: AGRT (n= 33) y AGDC (n= 36). El 100% del grupo con AGRT fue hospitalizado previamente por asma vs. 87,8% del grupo con AGDC (p= 0,03). El 63% del grupo AGRT requirió cuidados intensivos (UCI)), 82%, asistencia ventilatoria y uno fue traqueostomizado. En el AGDC, 54% requirió internación en la UCI , y 33%, asistencia ventilatoria (p= 0,03). La espirometría basal fue normal en el AGDC; se observó incapacidad ventilatoria obstructiva leve en el AGRT (p= 0,009). En el AGDC, hubo menor cumplimiento del tratamiento (p= 0,01). Se requirieron dosis mayores de corticoides inhalados en AGRT (p= 0,0001). Omalizumab fue indicado en AGRT (p= 0,0001). A los 6 meses de seguimiento, más del 75% de los niños en ambos grupos presentó asma controlada. Conclusiones. Se observó significativa falta de adherencia al tratamiento en el grupo AGDC. Se redujeron las dosis de tratamiento en este grupo. Se logró controlar la enfermedad en un alto porcentaje de niños con AGRT y AGDC.

Introduction. Severe asthma accounts for 5-7% of all asthma cases. The World Health Organization proposed a follow-up protocol to classify cases into severe, treatment-resistant asthma (STRA) or severe, difficult-to-control asthma (SDCA). Objective. To analyze the clinical, functional, and therapeutic characteristics of patients with STRA or SDCA. Methods. Cross-sectional, observational, and analytical study to assess the diagnosis, the extent of control (clinical and functional), comorbidities, treatment adherence, inhalation technique, and environmental factors in patients with severe asthma. Results. A total of 69 patients were included: STRA (n= 33) and SDCA (n= 36). In the group with STRA, 100% of patients had been previously hospitalized due to asthma compared to 87.8% in the group with SDCA (p= 0.03). In the group with STRA, 63% required admission to the intensive care unit (ICU); 82%, ventilatory support; and 1 patient, tracheostomy. In the group with SDCA, 54% required admission to the ICU; and 33%, ventilatory support (p= 0.03). The baseline spirometry was normal in the SDCA group; a mild obstructive ventilatory defect was observed in the STRA group (p= 0.009). In the SDCA group, treatment adherence was lower (p= 0.01). Higher inhaled corticosteroid doses were required in the STRA group (p= 0.0001). Omalizumab was indicated in the case of STRA (p= 0.0001). After 6 months of follow-up, more than 75% of children in both groups achieved asthma control. Conclusions. A significant lack of treatment adherence was observed in the SDCA group. In this group, treatment doses were reduced. Asthma was controlled in a high percentage of children with STRA and SDCA.