Identification of biomarkers for disease severity in nasopharyngeal secretions of infants with upper or lower respiratory tract viral infections.

Lower respiratory tract infections (LRTIs) produced by viruses are the most frequent cause of morbidity and mortality in children younger than 5 years of age. The immune response triggered by viral infection can induce a strong inflammation in the airways and cytokines could be considered as biomarkers for disease severity as these molecules modulate the inflammatory response that defines the outcome of patients. Aiming to predict the severity of disease during respiratory tract infections, we conducted a 1-year follow-up observational study in infants who presented upper or lower respiratory tract infections caused by seasonal respiratory viruses. At the time of enrollment, nasopharyngeal swabs (NPS) were obtained from infants to measure mRNA expression and protein levels of IL-3, IL-8, IL-33, and thymic stromal lymphopoietin. While all cytokines significantly increased their protein levels in infants with upper and lower respiratory tract infections as compared to control infants, IL-33 and IL-8 showed a significant increase in respiratory syncytial virus (RSV)-infected patients with LRTI as compared to patients with upper respiratory tract infection. We also found higher viral loads of RSV-positive samples with a greater IL-8 response at the beginning of the symptoms. Data obtained in this study suggest that both IL-8 and IL-33 could be used as biomarkers for clinical severity for infants suffering from LRTIs caused by the RSV.

Monitorización cardio respiratoria domiciliaria en lactantes / Home respiratory cardio monitoring in infants

Home cardio-respiratory monitoring began over 40 years ago with the aim of preventing sudden infant death. Although it has been shown that monitoring does not meet this objective, its prescription has been maintained in various clinical situations and with very different criteria. Consensus on the subject has not been able to define precisely the type of monitoring or the time required for different diseases. Among the diseases that still consider the indication of cardio-respiratory monitoring at home are: persistent apnea of prematurity, high-risk BRUE (Brief Resolved Unexplained Events), neurological or metabolic diseases with compromise of the respiratory center, convulsive cough, pathologic gastroesophageal reflux and technology-dependent patients (high flow nasal cannula (CNAF), noninvasive ventilation (NIV), invasive mechanical ventilation (IMV) to tracheostomy, and others). A review is presented on the development of cardio-respiratory monitoring at home, highlighting the true usefulness of this technology with a general proposal, which must be evaluated on a case-by-case basis and always taking into account the conditions that must be met to perform adequate monitoring and useful.

La monitorización cardio-respiratoria en domicilio se inició hace más de 40 años con el objetivo de prevenir la muerte súbita del lactante. Aun cuando se ha demostrado que la monitorización no cumple este objetivo, se ha mantenido su prescripción en diversas situaciones clínicas y con criterios muy diversos. Consensos acerca del tema no han llegado a definir con precisión el tipo de monitorización ni el tiempo requerido para distintas enfermedades. Dentro de las enfermedades que todavía consideran la indicación de monitorización cardio-respiratoria en domicilio se encuentran: apnea persistente del prematuro, BRUE (episodio breve resuelto inexplicado) de alto riesgo, enfermedades neurológicas o metabólicas con compromiso del centro respiratorio, tos convulsiva, reflujo gastroesofágico patológico y pacientes dependientes de tecnología (cánula nasal de alto flujo (CNAF), ventilación no invasiva (VNI), ventilación mecánica invasiva (VMI) a traqueostomía, y otros). Se presenta una revisión sobre el desarrollo de la monitorización cardio-respiratoria en domicilio, resaltando la verdadera utilidad que tendría esta tecnología con una propuesta general, que debe evaluarse caso a caso y siempre teniendo en cuenta las condiciones que deben cumplirse para realizar una monitorización adecuada y útil.

Cytokines in the Respiratory Airway as Biomarkers of Severity and Prognosis for Respiratory Syncytial Virus Infection: An Update.

The human respiratory syncytial virus (hRSV) is one of the most important causes of upper and lower respiratory tract infections in children and the main cause of bronchiolitis worldwide. Disease manifestations caused by hRSV may vary from mild to severe, occasionally requiring admission and hospitalization in intensive care units. Despite the high morbidity rates associated to bronchiolitis, treatment options against hRSV are limited and there are no current vaccination strategies to prevent infection. Importantly, the early identification of high-risk patients can help improve disease management and prevent complications associated with hRSV infection. Recently, the characterization of pro- and anti-inflammatory cytokine patterns produced during hRSV-related inflammatory processes has allowed the identification of potential prognosis biomarkers. A suitable biomarker should allow predicting the severity of the infection in a simple and opportune manner and should ideally be obtained from non-invasive samples. Among the cytokines associated with hRSV disease severity, IL-8, interferon-alpha (IFN-alpha), and IL-6, as well as the Th2-type cytokines thymic stromal lymphopoietin (TSLP), IL-3, and IL-33 have been highlighted as molecules with prognostic value in hRSV infections. In this review, we discuss current studies that describe molecules produced by patients during hRSV infection and their potential as biomarkers to anticipate the severity of the disease caused by this virus.

Evaluación de la disnea asociada al ejercicio / Exercise-induced dyspnea evaluation

Exercise-induced dyspnea is a common pediatric question but difficult to address since usually symptoms are described ambiguously by the child or parents. Most of times dyspnea is secondary to poor training but sometimes may be due to an underlying condition like exercise-induced bronchoconstriction or vocal cord dysfunction. To provide clinicians with a practical approach about exercise-induced dyspnea we have review pathogenesis and clinical characteristics of respiratory diseases and proposed an algorithm for study.

Frecuentemente nos vemos enfrentados a evaluar un niño con síntomas vagos asociados al ejercicio que el mismo paciente o sus padres describen como ahogo o sensación de pecho apretado. La mayoría de las veces se trata de cansancio atribuible al ejercicio normal que solo refleja pobre condicionamiento físico del individuo; sin embargo, este cansancio puede ser desproporcionado al esfuerzo, lo que obliga a considerar enfermedades comunes como asma o poco comunes como disfunción de cuerdas vocales. El objetivo de esta revisión es actualizar el conocimiento aquellas enfermedades respiratorias que forman parte del diagnóstico diferencial de la disnea asociada al ejercicio y proponer un algoritmo de estudio que permita un acercamiento práctico según causas de origen.

Evaluation of monoclonal antibodies that detect conserved proteins from Respiratory Syncytial Virus, Metapneumovirus and Adenovirus in human samples.

Human Respiratory Syncytial Virus (hRSV), human Metapneumovirus (hMPV) and Adenovirus (ADV), are three of the most prevalent viruses responsible for pneumonia and bronchiolitis in children and elderly worldwide, accounting for a high number of hospitalizations annually. Diagnosis of these viruses is required to take clinical actions that allow an appropriate patient management. Thereby, new strategies to design fast diagnostic methods are highly required. In the present work, six monoclonal antibodies (mAbs, two for each virus) specific for conserved proteins from hRSV, hMPV and ADV were generated and evaluated through different immunological techniques, based on detection of purified protein, viral particles and human samples. In vitro evaluation of these antibodies showed higher specificity and sensitivity than commercial antibodies tested in this study. These antibodies were used to design a sandwich ELISA tests that allowed the detection of hRSV, hMPV, and ADV in human nasopharyngeal swabs. We observed that hRSV and ADV were detected with sensitivity and specificity equivalent to a current Direct Fluorescence Assay (DFA) methodology. However, hMPV was detected with more sensitivity than DFA. Our data suggest that these new mAbs can efficiently identify infected samples and discriminate from patients infected with other respiratory pathogens.

Valores espirométricos en niños y adolescentes chilenos sanos / Spirometric values in healthy Chilean children and adolescents

Background: Spirometric flow and volume measurement are essential to evaluate patients with pulmonary disease. In Chile, several reference equations are used. Aim: To measure flow and expiratory volumes in healthy children and adolescents and compare their results with theoretical values according to Knudson, Quanjer, Gutierrez and NANHES III. Subjects and Methods: Spirometries were performed according to international standards in 1589 healthy children and adolescents aged 6 to 18 years (861 females) who lived in Santiago, Chile. Results: The obtained values for forced vital capacity, expiratory volume in one second, peak expiratory flow, were significantly higher than those calculated according to the above mentioned standards (p < 0.0001) with differences up to 18.7%. We constructed reference formulas for ages ranging from 6 to 18 years, separated by gender, using age, weight and height as independent variables. The latter had the greater influence on formula construction. Conclusions: The use of these new local formulas with allow the correct interpretation of spirometric results obtained in Chilean children and adolescents.

Elevated IL-3 and IL-12p40 levels in the lower airway of infants with RSV-induced bronchiolitis correlate with recurrent wheezing.

Respiratory Syncytial Virus (RSV) is the first cause of hospitalization due to bronchiolitis in infants. RSV bronchiolitis has been linked to asthma and recurrent wheezing, however the mechanisms behind this association have not been elucidated. Here, we evaluated the cytokine and chemokine profiles in the airways in infants with RSV bronchiolitis. Nasopharyngeal Aspirates (NPA) and Bronchoalveolar Lavage Fluids (BALF) from infants hospitalized due to RSV bronchiolitis and healthy controls were analyzed for cytokine and chemokine production. We observed elevated levels of Th2 cytokines (IL-3, IL-4, IL-10 and IL-13), pro-inflammatory cytokines and chemokines (IL-1ß, IL-6, TNF-ß, MCP-1/CCL2, MIP-1α/CCL3 and IL-8/CXCL8) in BALF from infants with RSV bronchiolitis, as compared to controls. We found a direct correlation of IL-3 and IL-12p40 levels with the development of recurrent wheezing later in life. These results suggest that IL-3 and IL-12p40 could be considered as molecular predictors for recurrent wheezing due to RSV infection.

Neumonía por bacterias atípicas: mycoplasma y Chlamydia pneumoniae ¿qué elementos tenemos para hacer un diagnóstico adecuado y decidir cuándo tratar? / Atypical pneumonia: mycoplasma and chlamydia pneumoniae: making an accurate diagnosis and deciding when to treat

Atypical Pneumonia has been studied for many years. Most clinically relevant atypical organisms involved in pneumonia in children are Mycoplasma pneumoniae and Chlamydia pneumoniae. Although great progress has been reached in new techniques, still there is no good tool, neither standardized nor accurate for a definitive diagnosis. In other hand, antibiotic therapy is under review due to contradictory evidence to support their use. We present a critical view of actual knowledge and propose an algorithm to proceed in clinical ground.

La neumonía por bacterias atípicas es sujeto de estudio desde hace años. Dentro de las bacterias atípicas más frecuentes y clínicamente relevantes en niños se reconocen Mycoplasma pneumoniae y Chlamydia pneumoniae. A pesar del aumento en el conocimiento de estas infecciones y avance en las técnicas diagnósticas, aun no contamos con una herramienta estandarizada y confiable que permita realizar un adecuado diagnóstico. Por otra parte, la necesidad real de efectuar un tratamiento antibiótico sigue siendo tema de discusión. Se presenta a continuación una revisión crítica del conocimiento actual y una propuesta de su enfrentamiento clínico.

[Spirometric values in healthy Chilean children and adolescents]. / Valores espirométricos en niños y adolescentes chilenos sanos.

BACKGROUND: Spirometric flow and volume measurement are essential to evaluate patients with pulmonary disease. In Chile, several reference equations are used. AIM: To measure flow and expiratory volumes in healthy children and adolescents and compare their results with theoretical values according to Knudson, Quanjer, Gutierrez and NANHES III. SUBJECTS AND METHODS: Spirometries were performed according to international standards in 1589 healthy children and adolescents aged 6 to 18 years (861 females) who lived in Santiago, Chile. RESULTS: The obtained values for forced vital capacity, expiratory volume in one second, peak expiratory flow, were significantly higher than those calculated according to the above mentioned standards (p < 0.0001) with differences up to 18.7%. We constructed reference formulas for ages ranging from 6 to 18 years, separated by gender, using age, weight and height as independent variables. The latter had the greater influence on formula construction. CONCLUSIONS: The use of these new local formulas with allow the correct interpretation of spirometric results obtained in Chilean children and adolescents.

[Prevalence of sudden death syndrome among children]. / Síndrome de muerte súbita del lactante: prevalencia y cambios en los últimos años en Chile.

BACKGROUND: The sudden infant's death syndrome (SD) is the leading cause of death in children under one year. Despite advances in its study, the pathogenesis has not been yet fully elucidated. AIM: To assess the prevalence of SD in Chilean infants and its changes in recent years. MATERIAL AND METHODS: Review of birth and death databases of the Ministry of Health from 1997 to 2009. All cases diagnosed as SD, according to the lnternational Classification of Diseases, 10th edition, were selected. A demographic analysis was performed and mortality rates for each year were calculated. RESULTS: We identified 1442 cases of SD (847 males, 517 deaths at home). The median age of death was 2 months (0 to 11.0 months). Ninety six percent of deaths occurred in children aged <6 months. Mortality rate for SD was 0.45/1000 live births. There was a 23% reduction between 1997 and 2009. When analyzing geographic distribution, more cases were found in the Southern latitudes of the country. CONCLUSIONS: The overall rate of SD in Chile is higher than in European countries and in North America. The observed decrease in cases over the years is still far from optimal.

Síndrome de muerte súbita del lactante: prevalencia y cambios en los últimos años en Chile / Prevalence of sudden death syndrome among children

Background: The sudden infant's death syndrome (SD) is the leading cause of death in children under one year. Despite advances in its study, the pathogenesis has not been yet fully elucidated. Aim: To assess the prevalence of SD in Chilean infants and its changes in recent years. Material and Methods: Review of birth and death databases of the Ministry of Health from 1997 to 2009. All cases diagnosed as SD, according to the lnternational Classification of Diseases, 10th edition, were selected. A demographic analysis was performed and mortality rates for each year were calculated. Results: We identified 1442 cases of SD (847 males, 517 deaths at home). The median age of death was 2 months (0 to 11.0 months). Ninety six percent of deaths occurred in children aged <6 months. Mortality rate for SD was 0.45/1000 live births. There was a 23% reduction between 1997 and 2009. When analyzing geographic distribution, more cases were found in the Southern latitudes of the country. Conclusions: The overall rate of SD in Chile is higher than in European countries and in North America. The observed decrease in cases over the years is still far from optimal.

Prevalence of habitual snoring and associated neurocognitive consequences among Chilean school aged children.

OBJECTIVE: To assess the prevalence of habitual snoring and symptoms of sleep disordered breathing (SDB) and their association with neurocognitive consequences in school-aged children. METHODS: A population based cross-sectional study was carried out in a low income urban setting in Santiago, Chile. A parental SDB-questionnaire was adapted and applied to a community based sample of children aged 7-17 years. Hyperactive/inattentive behavior was assessed using the Conner's rating scale. School grades were obtained and the associations between questionnaire's results and risks for poor academic performance were investigated. RESULTS: Of 700 questionnaires sent; 523 (75%) returned correctly filled in. Mean age of the subjects was 11.0±2.5 years; 246 (47%) were boys. Prevalence of habitual snoring was 18%. The Conner's rating scale correlated significantly with the SDB-questionnaire's score (r(s)=0.47). Children with habitual snoring showed significantly lower (mean±standard deviation) school grades in Spanish language (5.6±1.2 vs. 5.4±0.9, p-value=0.04) and general average school grades (5.9±0.6 vs. 5.7±0.6, p-value=0.05). After adjustment for possible confounding factors, children with an abnormal SDB questionnaire score had significantly higher risk for poor academic performance in Spanish language, odds ratio (95% confidence interval): 1.82 (1.01-3.27) and physical education 1.85 (1.05-3.26). DISCUSSION: There was a high prevalence of habitual snoring and symptoms of SDB in this survey of Chilean children, being among the highest reported. The presence of habitual snoring and an abnormal SDB questionnaire were associated with poor academic performance and hyperactive behavior.

Vía aérea difícil / Difficult airway

Difficult airway is a life-threatening situation which compromises the permeability of the upper airway and thus adequate ventilation and oxygenation. Multiple factors, acute and chronic such as: infectious, neoplastic and trauma have been associated with critical airway. Morbidity and mortality related to a difficult airway management remains as a significant problem in children, so is essential for the pediatric health team to be trained to recognize and anticipate situations that in clinical practice might determine a critical airway. The aim of this review is to provide concepts and guidance to assess patients with potentially difficult airway.

Una vía aérea difícil condiciona una situación con riesgo vital, ya que pone en peligro la permeabilidad de la vía aérea superior y con esto la capacidad de mantener una adecuada ventilación y oxigenación. Múltiples factores, tanto agudos como crónicos, entre ellos factores anatómicos propios del niño/a, complicaciones infecciosas, neoplásicas y/o traumáticas se han asociado con una vía aérea crítica. La morbilidad y mortalidad asociada al manejo inadecuado de esta condición continua siendo un problema significativo en la edad pediátrica; siendo fundamental que el equipo de salud se encuentre entrenado en reconocer y anticipar situaciones que en la práctica clínica podrían asociarse con una vía aérea difícil o crítica. El objetivo de la presente revisión es otorgar conceptos y una orientación en el enfrentamiento de los pacientes con una vía aérea potencialmente difícil.

Efectos clínicos de la exposición directa e indirecta a tabaco en los niños / Health effects of passive smoking exposure on children

El tabaquismo es fuente importante de contaminación intra domiciliaria. La prevención de la exposición al humo de tabaco tiene un impacto significativo en morbilidad y mortalidad en aquellos expuestos en forma indirecta, especialmente cuando se trata de un individuo en desarrollo activo como ocurre en la vida intrauterina y durante los primeros años de vida. La evidencia es contundente respecto del riesgo que existe en la disminución de la función pulmonar, aparición de sibilancias recurrentes, asma, neumonía y muerte súbita. La exposición al humo de tabaco en los niños debe recibir mayor atención de parte del equipo de salud, especialmente del pediatra.

Guía clínica para el diagnóstico y cuidado de niños/adolescentes con bronquiolitis obliterante post-infecciosa, 2009 / Clinical guidelines for the diagnosis and care of children and adolescents with post-infectious bronchiolitis obliterans, 2009

La bronquiolitis obliterante (BO) es un síndrome clínico poco frecuente en niños, caracterizado por la obstrucción crónica al flujo de aire asociado a cambios inflamatorios y distintos grados de fibrosis en la vía aérea pequeña. Si bien existen muchas etiologías, la causa mas frecuente se asocia a infeccionesrespiratorias virales, principalmente adenovirus. No existe un consenso para establecer su diagnóstico; sin embargo, se considera un espectro de síntomas persistentes asociados a un patrón en mosaico, bronquiectasias y atelectasias persistentes. El rol de la biopsia pulmonar ha sido cuestionado por subajo rendimiento, invasividad y complicaciones. No existe un tratamiento específico por lo que elmanejo es soporte. Probablemente la mejor estrategia constituya el empleo de antibióticos en forma agresiva, soporte kinésico y nutricional constante y una precoz rehabilitación pulmonar. Estas guías clínicas representan un esfuerzo multidisciplinario, basado en evidencias actuales para brindarherramientas prácticas para el diagnóstico y cuidado de niños y adolescentes con BO post infecciosa.

Flexible fiberoptic bronchoscopy in children with heart diseases: a twelve years experience.

In children, cardiac diseases and respiratory disorders are tightly linked entities whose evaluation should be performed integrally. Flexible fiberoptic bronchoscopy (FB) presents a diagnostic and therapeutic role by assessing the airway anatomically, dynamically, and through the performance of several procedures. The present study describes our experience on FB assessment in children with congenital and acquired cardiac diseases, providing a characterization of the principal demographic and clinical features. Records of 72 patients under 14 years (mean age 21 months) with heart diseases, corresponding to 104 FB performed between January 1993 and October 2004 were reviewed. The principal cardiac diseases were left-to-right shunt (51.9%), followed by right-to-left shunt (17.3%) and miscellaneous cardiopathies (8.7%). The main indications for FB assessment were study of atelectasis (35%), stridor (14%), and pneumonia (14%). Airway malacias, as a group, were the commonest finding, represented mainly by left main bronchus malacia (24%). The second most common finding was stenosis by extrinsic compression, and among these, 75% corresponded to left main bronchus compression. Sixteen different types of clinically meaningful utilities were obtained. No mortality was reported and in only one procedure was there a major complication, which was easily managed. We concluded that FB is an important and safe diagnostic-therapeutic tool in the health care of neonates, infants, and children with a variety of cardiac diseases.

[Empyema and pleural effusion in children]. / Empiema y efusión pleural en niños.

INTRODUCTION: Pleural empyema (PE) is a serious complication of community-acquired pneumonia (CAP). OBJECTIVES: To describe the clinical profile of hospitalized patients with PE in the pediatric ward of the Catholic University Hospital between 2000-2005. PATIENTS AND METHODS: Retrospectively, all pediatric admission due to CAP and pleural effusion (86 children) were identified. In 59 (70%) children > 1 thoracocentesis were performed. We considered PE as the presence in the pleural effusion of pus, and/or a positive gram strain and/ or positive culture, and/or a pH < 7.10. Children with effusions not meeting any criteria were used as controls. RESULTS: Twenty four PE and 25 controls were identified, with a global mean age of 2.9 years (range: 8 months to 14.3 years); 78% were < 5 years, with a significant difference between PE and controls [1.6 vs 3.3 years (p = 0.01)]. The mean duration of symptoms in PE patients before admission was 7 days (range: 2-21), and the most frequent symptoms were fever (100%) and cough (96%). In 15/24 cases a microorganism was identified being Streptococcus pneumoniae (n = 9) the most common. In 48 patients management was conservative and in 4 surgical procedures were required. The mean duration of hospitalization was significantly higher in the PE group vs controls group: 15 (range: 5-38) vs 9 days (range 3-16) (p < 0.01). A chest tube was inserted in 83% of children with EP compared with 36% in the control group (p = 0.002). There were no difference in number of days of oxygen use [6 vs 4.5 (p = 0.36)] or number of chest tubes per child [3 vs 2.5 (p = 0.29)]. No deaths were reported. CONCLUSION: PE in children represented an acute respiratory event associated with more prolonged hospitalization especially at younger ages; the majority of cases did not require surgical intervention.

Soporte ventilatorio no invasivo en enfermedades neuromusculares / Noninvasive ventilation in neuromuscular disease

Las enfermedades neuromusculares (ENM) comprenden un extenso grupo de condiciones neurológicas que comprometen la eficacia del sistema respiratorio y que generalmente se asocian a síndromes de hipoventilación. El curso de muchas es inexorablemente hacia la insuficiencia respiratoria y muerte; sin embargo, su evolución depende de diversos factores. El soporte ventilatorio crónico mediante CPAP o BiPAP en niños con ENM ha demostrado el retiro de pacientes de la ventilación mecánica convencional, disminuir el número de complicaciones asociadas a infecciones, intubación prolongada de la vía aérea y traqueostomía. El incremento en la sobrevida de los pacientes con ENM progresivas ha permitido que muchos de estos pacientes permanezcan en sus domicilios. En general el empleo de máscaras es seguro, por lo que las complicaciones mayores son infrecuentes. El pronóstico de las ENM dependerá del grado de compromiso de los distintos elementos respiratorios, existiendo una estrecha relación con xifoescoliosis.

[Exercise-induced asthma as perceived by pediatric patients and their parents]. / Asma inducida por ejercicio: Diferencias en la percepciónde síntomas entre pacientes pediátricos y sus padres.

BACKGROUND: Exercise is a frequent trigger of symptoms in asthmatic children and it worsens their quality of life. AIM: To compare the perception about exercise among asthmatic pediatric patients and their parents. MATERIAL AND METHODS: Asthmatic patients with symptoms related to exercise, were tested with an exercise challenge test following the Tal protocol. Before testing, a questionnaire about symptoms triggered by exercise was answered by children and their parents. The data was analyzed with a Kappa correlation test. RESULTS: Seventy five patients, aged 6 to 15 years, were studied. Forty one percent exercised less than one hour per week. Although 64% reported to experience respiratory difficulty and 80% cough during exertion, 87% were willing to perform more exercise. Forty percent of all patients had a positive challenge test for exercise-induced asthma. Correlation between patient's and parent's answers about the effect of physical activity exercise was low, with a kappa of 0.53. There was no correlation between exercise test and the answers to the questionnaire. CONCLUSIONS: Children with asthma frequently have exercise-associated symptoms and parental perception about this problem is very low.

Diagnóstico / Diagnosis

Establecer el diagnóstico de asma en niños depende del escenario clínico de cada evaluación. Así, para efectos epidemiológicos la presencia de sibilancias recurrentes en los últimos doce meses es un criterio válido. Se reconoce que existen dificultades técnicas para establecer la presencia de inflamación crónica eosinofílica o determinar obstrucción bronquial en los flujos espiratorios especialmente en los niños menores de 5 años. El diagnóstico de asma es fundamentalmente clínico en base a la presencia de síntomas y signos. Siempre debe considerarse posibles diagnósticos alternativos así como la presencia de atopía.