Development of Lung Function in Preterm Infants During the First Two Years of Life.

INTRODUCTION: It remains unclear if prematurity itself can influence post delivery lung development and particularly, the bronchial size. AIM: To assess lung function during the first two years of life in healthy preterm infants and compare the measurements to those obtained in healthy term infants during the same time period. METHODS: This observational longitudinal study assessed lung function in 74 preterm (30+0 to 35+6 weeks' gestational age) and 76 healthy term control infants who were recruited between 2011 and 2013. Measurements of tidal breathing, passive respiratory mechanics, tidal and raised volume forced expirations (V'maxFRC and FEF25-75, respectively) were undertaken following administration of oral chloral hydrate sedation according to ATS/ERS recommendations at 6- and 18-months corrected age. RESULTS: Lung function measurements were obtained from the preterm infants and full term controls initially at 6 months of age. Preterm infants had lower absolute and adjusted values (for gestational age, postnatal age, sex, body size, and confounding factors) for respiratory compliance and V'maxFRC. At 18 months corrected postnatal age, similar measurements were repeated in 57 preterm infants and 61 term controls. A catch-up in tidal volume, respiratory mechanics parameters, FEV0.5 and forced expiratory flows was seen in preterm infants. CONCLUSION: When compared with term controls, the lower forced expiratory flows observed in the healthy preterm group at 6 months was no longer evident at 18 months corrected age, suggesting a catch-up growth of airway function.

Development of Lung Function in Preterm Infants During the First Two Years of Life / Desarrollo de la función pulmonar en lactantes pretérmino durante los 2 primeros años de vida

Introduction: It remains unclear if prematurity itself can influence post delivery lung development and particularly, the bronchial size.AimTo assess lung function during the first two years of life in healthy preterm infants and compare the measurements to those obtained in healthy term infants during the same time period.MethodsThis observational longitudinal study assessed lung function in 74 preterm (30+0 to 35+6 weeks’ gestational age) and 76 healthy term control infants who were recruited between 2011 and 2013. Measurements of tidal breathing, passive respiratory mechanics, tidal and raised volume forced expirations (V’maxFRC and FEF25–75, respectively) were undertaken following administration of oral chloral hydrate sedation according to ATS/ERS recommendations at 6- and 18-months corrected age.ResultsLung function measurements were obtained from the preterm infants and full term controls initially at 6 months of age. Preterm infants had lower absolute and adjusted values (for gestational age, postnatal age, sex, body size, and confounding factors) for respiratory compliance and V’maxFRC. At 18 months corrected postnatal age, similar measurements were repeated in 57 preterm infants and 61 term controls. A catch-up in tidal volume, respiratory mechanics parameters, FEV0.5 and forced expiratory flows was seen in preterm infants.ConclusionWhen compared with term controls, the lower forced expiratory flows observed in the healthy preterm group at 6 months was no longer evident at 18 months corrected age, suggesting a catch-up growth of airway function. (AU)

Introducción: Todavía no está claro si la prematuridad por sí sola puede tener influencia en el desarrollo pulmonar tras el parto y, en particular, en el tamaño bronquial.ObjetivoValorar la función pulmonar durante los 2 primeros años de vida en lactantes pretérmino sanos y comparar las medidas con las obtenidas en lactantes nacidos a término sanos durante el mismo periodo de tiempo.MétodosEste ensayo longitudinal observacional valoró la función pulmonar en 74 lactantes pretérmino (30+0 a 35+6 semanas de edad gestacional) y 76 lactantes nacidos a término sanos como controles, que se seleccionaron entre 2011 y 2013. Se llevaron a cabo las mediciones de la respiración corriente, la mecánica respiratoria pasiva, los flujos espiratorios forzados a volumen corriente y con insuflación previa (V’maxFRC y FEF25-75, respectivamente) tras la sedación con hidrato de cloral siguiendo las recomendaciones de las ATS/ERS a la edad corregida de 6 y 18 meses.ResultadosInicialmente se obtuvieron las medidas de función pulmonar de los lactantes pretérmino y los controles a término a los 6 meses de edad. Los lactantes pretérmino presentaron unos valores absolutos y ajustados (a la edad gestacional, la edad posnatal, el sexo, el tamaño corporal y los factores de confusión) menores para la distensibilidad pulmonar y la V’maxFRC. A los 18 meses de edad posnatal corregida, se repitieron las mismas mediciones en 57 lactantes pretérmino y 61 controles a término. Se observó una recuperación del volumen corriente, los parámetros de mecánica respiratoria, el FEV0,5 y los flujos espiratorios forzados en los lactantes pretérmino.ConclusiónEn comparación con los controles a término, los flujos espiratorios forzados más bajos observados en el grupo de pretérminos sanos a los 6 meses no se observaron a los 18 meses de edad corregida, lo que evidencia un crecimiento de recuperación de la función de la vía respiratoria. (AU)

Recurrent wheezing during the first 3 years of life in a birth cohort of moderate-to-late preterm infants.

BACKGROUND: Data addressing short- and long-term respiratory morbidity in moderate-late preterm infants are limited. We aim to determine the incidence of recurrent wheezing and associated risk and protective factors in these infants during the first 3 years of life. METHODS: Prospective, multicenter birth cohort study of infants born at 32+0 to 35+0  weeks' gestation and followed for 3 years to assess the incidence of physician-diagnosed recurrent wheezing. Allergen sensitization and pulmonary function were also studied. We used multivariate mixed-effects models to identify risk factors associated with recurrent wheezing. RESULTS: A total of 977 preterm infants were enrolled. Rates of recurrent wheezing during year (Y)1 and Y2 were similar (19%) but decreased to 13.3% in Y3. Related hospitalizations significantly declined from 6.3% in Y1 to 0.75% in Y3. Independent risk factors for recurrent wheezing during Y2 and Y3 included the following: day care attendance, acetaminophen use during pregnancy, and need for mechanical ventilation. Atopic dermatitis on Y2 and male sex on Y3 were also independently associated with recurrent wheezing. Palivizumab prophylaxis for RSV during the first year of life decreased the risk or recurrent wheezing on Y3. While there were no differences in rates of allergen sensitization, pulmonary function tests (FEV0.5 ) were significantly lower in children who developed recurrent wheezing. CONCLUSIONS: In moderate-to-late premature infants, respiratory symptoms were associated with lung morbidity persisted during the first 3 years of life and were associated with abnormal pulmonary function tests. Only anti-RSV prophylaxis exerted a protective effect in the development of recurrent wheezing.

Disfunción de la pequeña vía aérea en niños con asma controlada / Small Airway Dysfunction in Children With Controlled Asthma

Introducción: El asma se caracteriza por una inflamación crónica de las vías respiratorias centrales y distales. El objetivo de este estudio ha sido evaluar la vía aérea pequeña (VAP) en niños con asma moderada y/o grave con FEV1 normal. Métodos: Estudio abierto, prospectivo, observacional y transversal con inclusión consecutiva de casos con asma moderada o grave, bajo tratamiento clínico habitual con FEV1 basal normal. Se ha determinado la FEno a flujos múltiples (CAno), resistencias y reactancia oscilatorias (R5-R20, X5), espirometría forzada (FEV1, FEF25-75), pletismografía corporal total (RV/TLC) y prueba de broncodilatación. La afectación de la VAP se definió por: Cano > 4,5 ppb, R5-R20 > 0,147kPa/L/s, X5 <-0,18kPa/L, FEF25-75 < -1,65 z-score, RV/TL > 33%. El mal control de asma se definió por ≤ 19 puntos en el cuestionario ACT o ≤ 20 en c-ACT. Resultados: Cohorte de 100 casos, 76 con asma moderada y 24 con asma grave, 71 niños clasificados como mal controlados y 29 bien controlados. El 77,78% del grupo con todas las determinaciones correctas (n =7 2) mostró ≥ 1 parámetro alterado de VAP y el 48,61% ≥ 2 parámetros. No hubo diferencias entre los casos bien y mal controlados. Conclusiones: Los niños con asma moderada y grave, con el FEV1 preservado, muestran un fenotipo de VAP disfuncionante. En nuestra muestra, la evaluación de la VAP mediante las técnicas descritas, no aporta información sobre el control habitual de la enfermedad

Introduction: Asthma is characterized by chronic inflammation of the central and distal airways. The aim of this study was to assess the small airway (SA) of children with moderate-severe asthma with normal FEV1. Methods: This was an open-label, prospective, observational, cross-sectional study with consecutive inclusion of patients with moderate-severe asthma, receiving standard clinical treatment, with normal baseline FEV1. We determined multiflow FEno (CAno), oscillatory resistance and reactance (R5-R20, X5), forced spirometry (FEV1, FEF25-75), total body plethysmography (RV/TLC) and bronchodilation test. SA involvement was defined as: Cano > 4.5 ppb, R5-R20 > 0.147kPa/L/s, X5< -0.18kPa/L, FEF25-75 < -1.65 z-score, RV/TLC > 33%. Poor asthma control was defined as ≤ 19 points on the ACT questionnaire or ≤ 20 on the c-ACT. Results: In a cohort of 100 cases, 76 had moderate asthma and 24 had severe asthma; 71 children were classified as poorly controlled and 29 were well-controlled. In total, 77.78% of the group with all the correct determinations (n=72) showed ≥ 1 altered SA parameter and 48.61% ≥ 2 parameters. There were no differences between well-controlled or poorly controlled cases. Conclusions: Children with moderate-severe asthma, with normal FEV1, show a phenotype of dysfunctional SA. In our series, the evaluation of SA using the techniques described above did not provide information on disease control

Isolated pulmonary interstitial glycogenosis associated with alveolar growth abnormalities: A long-term follow-up study.

INTRODUCTION: Pulmonary interstitial glycogenosis (PIG) is a rare infant interstitial lung disease characterized by an increase in the number of interstitial mesenchymal cells, presenting as enhanced cytoplasmic glycogen, and is considered to represent the expression of an underlying lung development disorder. METHODS: This study describes the clinical, radiological, and functional characteristics and long-term outcomes (median 12 years) of nine infants diagnosed with isolated PIG associated with alveolar simplification in the absence of other diseases. RESULTS: All patients presented with tachypnea. Additionally, seven patients had breathing difficulties and hypoxemia. Abnormalities in chest-computerized tomography (CT) with a pattern of ground-glass opacity, septal thickening, and air trapping were observed in all individuals, with images suggesting abnormal alveolar growth (parenchymal bands and architectural distortion). All lung biopsies showed alveolar simplification associated with an increased number of interstitial cells, which appeared as accumulated cytoplasmic glycogen. In the follow-up, all patients were asymptomatic. The respiratory function test was normal in only two patients. Five children showed an obstructive pattern, and two children showed a restrictive pattern. Chest-CT, performed after an average of 6.5 years since the initial investigation, revealed a partial improvement of the ground-glass opacity pattern; however, relevant alterations persisted. CONCLUSION: Although the patients with PIG in the absence of other associated pathologies had a good clinical outcome, significant radiographic alterations and sequelae in lung function were still observed after a median follow-up of 12 years, suggesting that PIG is a marker of some other persistent abnormalities in lung growth, which have effects beyond the symptomatic period.

Small Airway Dysfunction in Children With Controlled Asthma. / Disfunción de la pequeña vía aérea en niños con asma controlada.

INTRODUCTION: Asthma is characterized by chronic inflammation of the central and distal airways. The aim of this study was to assess the small airway (SA) of children with moderate-severe asthma with normal FEV1. METHODS: This was an open-label, prospective, observational, cross-sectional study with consecutive inclusion of patients with moderate-severe asthma, receiving standard clinical treatment, with normal baseline FEV1. We determined multiflow FEno (CAno), oscillatory resistance and reactance (R5-R20, X5), forced spirometry (FEV1, FEF25-75), total body plethysmography (RV/TLC) and bronchodilation test. SA involvement was defined as: CAno>4.5 ppb, R5-R20>0.147kPa/L/s, X5<-0.18kPa/L, FEF25-75<-1.65 z-score, RV/TLC>33%. Poor asthma control was defined as ≤ 19 points on the ACT questionnaire or ≤ 20 on the c-ACT. RESULTS: In a cohort of 100 cases, 76 had moderate asthma and 24 had severe asthma; 71 children were classified as poorly controlled and 29 were well-controlled. In total, 77.78% of the group with all the correct determinations (n=72) showed ≥ 1 altered SA parameter and 48.61% ≥ 2 parameters. There were no differences between well-controlled or poorly controlled cases. CONCLUSIONS: Children with moderate-severe asthma, with normal FEV1, show a phenotype of dysfunctional SA. In our series, the evaluation of SA using the techniques described above did not provide information on disease control.

Risk factors for bronchiolitis, recurrent wheezing, and related hospitalization in preterm infants during the first year of life.

BACKGROUND: Airway diseases are highly prevalent in infants and cause significant morbidity. We aimed to determine the incidence and risk factors for respiratory morbidity in a Spanish cohort of moderate-to-late preterm (MLP) infants prospectively followed during their first year of life. METHODS: SAREPREM is a multicenter, prospective, longitudinal study. Preterm infants born at 32-35 weeks of gestation with no comorbidities were enrolled within 2 weeks of life and followed at 2-4 weeks, 6, and 12 months of age. Multivariate mixed-models were performed to identify independent risk factors associated with (i) development of bronchiolitis, (ii) recurrent wheezing, or (iii) related hospital admissions. RESULTS: Overall, 977 preterm infants were included, and 766 (78.4%) completed follow-up. Of those, 365 (47.7%) developed bronchiolitis during the first year, 144 (18.8%) recurrent wheezing, and 48 (6.3%) were hospitalized. While low birthweight, day care attendance (DCA) and school-age siblings were significantly and independently associated with both the development of bronchiolitis and recurrent wheezing, lower maternal age increased the risk for bronchiolitis and respiratory-related hospitalizations. Lastly, mechanical ventilation was associated with a higher risk of bronchiolitis and history of asthma in any parent increased the likelihood of developing recurrent wheezing. CONCLUSIONS: In this study, several non-modifiable parameters (family history of asthma, low birthweight, need for mechanical ventilation) and modifiable parameters (young maternal age, DCA, or exposure to school-age siblings) were identified as significant risk factors for the development of bronchiolitis and recurrent wheezing during the first year of life in MLP infants.

Patrones inflamatorios en niños asmáticos basados en la determinación de óxido nítrico alveolar / Inflammatory Patterns in Asthmatic Children Based on Alveolar Nitric Oxide Determination

Introducción: El óxido nítrico (NO) puede medirse a nivel proximal (flujo máximo NO en vía aérea [J'awNO]) y distal (concentración alveolar de NO [CANO]). Se han descrito 4 patrones inflamatorios en asmáticos, aunque su relevancia no ha sido bien establecida. El objetivo ha sido determinar el J'awNO y la CANO para establecer 4 categorías inflamatorias en asmáticos. Material y métodos: Estudio transversal de una muestra de niños sanos y asmáticos. Determinación de NO exhalado a flujos múltiples. De acuerdo con el modelo bicompartimental se obtuvieron la CANOy el J'awNO. En asmáticos se realizó cuestionario de control de asma (CAN) y espirometría forzada. Categorización de pacientes en tipo i (J'awNO y CANO normal), tipo ii (J'awNO elevado y CANO normal), tipo iii (J'awNO y CANO elevados) y tipo iv (J'awNO normal y CANO elevado). Estudio de correlación entre FENO,50, J'awNO y CANO mediante R de Spearman. Análisis de la varianza y comparaciones pareadas, mediante corrección post hoc de Bonferroni. Resultados: Se estudiaron 162 niños: 49 (32,23%) controles sanos y 103 (67,76%) asmáticos. Se excluyeron 10 niños, 4 (2.4%) porque las eterminaciones fueron incorrectas y 6 (3,7%) porque las determinaciones no siguieron el modelo lineal (valores de CANO negativos). En controles la FENO,50 (ppb) (mediana y rango) fue 11,5 (1,6-27,3), J'awNO (pl/s) 516 (98,3-1.470) y CANO(ppb) 2,2 (0,1-4,5). De los asmáticos, 44 (42,7%) se categorizaron en tipo i, 41 (39,8%) en tipo ii, 14 (13,5%%) en tipo iii y 4 (3,88%) en tipo iv. Buena correlación entre J'awNO y FENO,50(r = 0,97). No hubo asociación entre J'awNO y CANO. Disminución significativa de FEV1/FVC en tipo iii (media 79,8 ± 7,5). La morbilidad fue significativamente superior en tipos iii y iv. Conclusiones: Los valores de normalidad obtenidos son similares a los previamente publicados. Los asmáticos con CANO elevado presentaron mayor morbilidad. No hay correlación entre inflamación proximal y distal

Introduction: Nitric oxide (NO) levels can be measured at proximal (maximum airway NO flux [J’awNO]) and distal (alveolar NO concentration [CANO]) levels. Four inflammatory patterns have been described in asthmatic individuals, although their relevance has not been well established. The objective was to determine J’awNO and CANO in order to establish four inflammatory categories in asthmatics. Material and methods: Cross-sectional study of a sample consisting of healthy and asthmatic children. Exhaled NO was determined at multiple flows. J’awNO and CANO were obtained according to the two-compartment model. The asthma control questionnaire (ACQ) and spirometry were administered to asthmatic children. Patients were categorized as type i (normal J’awNO and CANO), type ii (elevated J’awNO and normal CANO), type iii (elevated J’awNO and CANO) and type iv (normal J’awNO and elevated CANO). Correlation between FENO,50, J’awNO and CANO was analyzed using Spearman’s R Correlation Test. Analysis of variance and paired comparisons were performed using the Bonferroni correction. Results: One hundred sixty-two children were studied, of whom 49 (32.23%) were healthy controls and 103 (67.76%) asthmatics. In the control subjects, FENO,50 (ppb)(median and range) was 11.5 (1.6 to 27.3), J’awNO (pl/s) was 516 (98.3 to 1470) and CANO (ppb) was 2.2 (0.1 to 4.5). Forty-four (42.7%) of the asthmatic participants were categorized as type i, 41 (39.8%) as type ii, 14 (13.5%) as type iii and 4 (3.88%) as type iv. Good correlation was observed between J’awNO and FENO,50 (r = 0.97). There was no association between J’awNO and CANO. FEV1/FVC decreased significantly in type iii (mean 79.8 ± 7.5). Morbidity was significantly higher in types iii and iv. Conclusions: Normal values obtained are similar to those previously reported. Asthmatics with high CANO showed higher morbidity. No correlation was found between proximal and distal inflammation

Long-Term Burden and Respiratory Effects of Respiratory Syncytial Virus Hospitalization in Preterm Infants-The SPRING Study.

The health status of premature infants born 321-350 weeks' gestational age (wGA) hospitalized for RSV infection in the first year of life (cases; n = 125) was compared to that of premature infants not hospitalized for RSV (controls; n = 362) through 6 years. The primary endpoints were the percentage of children with wheezing between 2-6 years and lung function at 6 years of age. Secondary endpoints included quality of life, healthcare resource use, and allergic sensitization. A significantly higher proportion of cases than controls experienced recurrent wheezing through 6 years of age (46.7% vs. 27.4%; p = 0.001). The vast majority of lung function tests appeared normal at 6 years of age in both cohorts. In children with pulmonary function in the lower limit of normality (FEV1 Z-score [-2; -1]), wheezing was increased, particularly for cases vs. controls (72.7% vs. 18.9%, p = 0.002). Multivariate analysis revealed the most important factor for wheezing was RSV hospitalization. Quality of life on the respiratory subscale of the TAPQOL was significantly lower (p = 0.001) and healthcare resource utilization was significantly higher (p<0.001) in cases than controls. This study confirms RSV disease is associated with wheezing in 32-35 wGA infants through 6 years of age.

Inflammatory patterns in asthmatic children based on alveolar nitric oxide determination.

INTRODUCTION: Nitric oxide (NO) levels can be measured at proximal (maximum airway NO flux [J'aw(NO)]) and distal (alveolar NO concentration [C(ANO)]) levels. Four inflammatory patterns have been described in asthmatic individuals, although their relevance has not been well established. The objective was to determine J'aw(NO) and C(ANO) in order to establish four inflammatory categories in asthmatics. MATERIAL AND METHODS: Cross-sectional study of a sample consisting of healthy and asthmatic children. Exhaled NO was determined at multiple flows. J'aw(NO) and C(ANO) were obtained according to the two-compartment model. The asthma control questionnaire (ACQ) and spirometry were administered to asthmatic children. Patients were categorized as type I (normal J'aw(NO) and C(ANO)), type II (elevated J'aw(NO) and normal C(ANO)), type III (elevated J'aw(NO) and C(ANO)) and type IV (normal J'aw(NO) and elevated C(ANO)). Correlation between FE(NO,50), J'aw(NO) and C(ANO) was analyzed using Spearman's R Correlation Test. Analysis of variance and paired comparisons were performed using the Bonferroni correction. RESULTS: One hundred sixty-two children were studied, of whom 49 (32.23%) were healthy controls and 103 (67.76%) asthmatics. In the control subjects, FE(NO,50) (ppb)(median and range) was 11.5 (1.6 to 27.3), J'aw(NO) (pl/s) was 516 (98.3 to 1470) and C(ANO) (ppb) was 2.2 (0.1 to 4.5). Forty-four (42.7%) of the asthmatic participants were categorized as type I, 41 (39.8%) as type II, 14 (13.5%) as type III and 4 (3.88%) as type IV. Good correlation was observed between J'aw(NO) and FE(NO,50) (r=0.97). There was no association between J'aw(NO) and C(ANO). FEV1/FVC decreased significantly in type III (mean 79.8±7.5). Morbidity was significantly higher in types III and IV. CONCLUSIONS: Normal values obtained are similar to those previously reported. Asthmatics with high C(ANO) showed higher morbidity. No correlation was found between proximal and distal inflammation.

Social, economic, and health impact of the respiratory syncytial virus: a systematic search.

BACKGROUND: Bronchiolitis caused by the respiratory syncytial virus (RSV) and its related complications are common in infants born prematurely, with severe congenital heart disease, or bronchopulmonary dysplasia, as well as in immunosuppressed infants. There is a rich literature on the different aspects of RSV infection with a focus, for the most part, on specific risk populations. However, there is a need for a systematic global analysis of the impact of RSV infection in terms of use of resources and health impact on both children and adults. With this aim, we performed a systematic search of scientific evidence on the social, economic, and health impact of RSV infection. METHODS: A systematic search of the following databases was performed: MEDLINE, EMBASE, Spanish Medical Index, MEDES-MEDicina in Spanish, Cochrane Plus Library, and Google without time limits. We selected 421 abstracts based on the 6,598 articles identified. From these abstracts, 4 RSV experts selected the most relevant articles. They selected 65 articles. After reading the full articles, 23 of their references were also selected. Finally, one more article found through a literature information alert system was included. RESULTS: The information collected was summarized and organized into the following topics: 1. Impact on health (infections and respiratory complications, mid- to long-term lung function decline, recurrent wheezing, asthma, other complications such as otitis and rhino-conjunctivitis, and mortality; 2. Impact on resources (visits to primary care and specialists offices, emergency room visits, hospital admissions, ICU admissions, diagnostic tests, and treatments); 3. Impact on costs (direct and indirect costs); 4. Impact on quality of life; and 5. Strategies to reduce the impact (interventions on social and hygienic factors and prophylactic treatments). CONCLUSIONS: We concluded that 1. The health impact of RSV infection is relevant and goes beyond the acute episode phase; 2. The health impact of RSV infection on children is much better documented than the impact on adults; 3. Further research is needed on mid- and long-term impact of RSV infection on the adult population, especially those at high-risk; 4. There is a need for interventions aimed at reducing the impact of RSV infection by targeting health education, information, and prophylaxis in high-risk populations.

Urokinase versus VATS for treatment of empyema: a randomized multicenter clinical trial.

BACKGROUND AND OBJECTIVE: Parapneumonic empyema (PPE) is a frequent complication of acute bacterial pneumonia in children. There is limited evidence regarding the optimal treatment of this condition. The aim of this study was to compare the efficacy of drainage plus urokinase versus video-assisted thoracoscopic surgery in the treatment of PPE in childhood. METHODS: This prospective, randomized, multicenter clinical trial enrolled patients aged <15 years and hospitalized with septated PPE. Study patients were randomized to receive urokinase or thoracoscopy. The main outcome variable was the length of hospital stay after treatment. The secondary outcomes were total length of hospital stay, number of days with the chest drain, number of days with fever, and treatment failures. The trial was approved by the ethics committees of all the participating hospitals. RESULTS: A total of 103 patients were randomized to treatment and analyzed; 53 were treated with thoracoscopy and 50 with urokinase. There were no differences in demographic characteristics or in the main baseline characteristics between the 2 groups. No statistically significant differences were found between thoracoscopy and urokinase in the median postoperative stay (10 vs 9 days), median hospital stay (14 vs 13 days), or days febrile after treatment (4 vs 6 days). A second intervention was required in 15% of children in the thoracoscopy group versus 10% in the urokinase group (P = .47). CONCLUSIONS: Drainage plus urokinase instillation is as effective as video-assisted thoracoscopic surgery as first-line treatment of septated PPE in children.

Genetic characterization of historical epidemic mumps viruses in northern Spain, 1987-1990.

The mumps virus (MuV) is genetically diverse and is divided into 12 genotypes. The World Health Organization has recommended expanding virological surveillance for MuV, and therefore molecular characterization of circulating strains (i.e. genotypes) is increasingly performed. Nevertheless, little is known about the genotypes circulating before the massive vaccination of children and adolescents. The present study analyzed the strains causing the 1988-1989 mumps epidemic in the Basque Country, northern Spain, which occurred in the early vaccination period, before the endemic circulation of mumps virus was blocked. The epidemic reached an annual incidence rate of more than 400 cases/100,000 inhabitants, and caused a large number of cases of mumps meningitis. MuV RNA was amplified from the cerebrospinal fluid of 15 infected patients during the epidemic and from three more patients affected shortly before or after this epidemic (1987, early 1988 and 1990). Genotyping of the complete small hydrophobic gene (316 nucleotides), amplified in the 18 strains, as well as of the entire hemagglutinin-neuraminidase gene (1749 nucleotides), amplified in four strains, assigned all strains to genotype K, a genotype infrequently detected at present. Although the putative HN protein sequence differed by 4.8-5.5% in relation to Jeryl Lynn 5 strain (the main strain used in the vaccination program in this region), the vaccine was effective, and dramatically reduced the incidence of mumps over the following years. The presence of genotype K strains in Spain in the 1980s, together with their contemporary detection in Scandinavia, suggests that this genotype could have caused the Spanish epidemic and was also circulating widely in Europe at that time.

Alveolar nitric oxide and its role in pediatric asthma control assessment.

BACKGROUND: Nitric oxide can be measured at multiple flow rates to determine proximal (maximum airway nitric oxide flux; JawNO) and distal inflammation (alveolar nitric oxide concentration; CANO). The main aim was to study the association among symptoms, lung function, proximal (maximum airway nitric oxide flux) and distal (alveolar nitric oxide concentration) airway inflammation in asthmatic children treated and not treated with inhaled glucocorticoids. METHODS: A cross-sectional study with prospective data collection was carried out in a consecutive sample of girls and boys aged between 6 and 16 years with a medical diagnosis of asthma. Maximum airway nitric oxide flux and alveolar nitric oxide concentration were calculated according to the two-compartment model. In asthmatic patients, the asthma control questionnaire (CAN) was completed and forced spirometry was performed. In controls, differences between the sexes in alveolar nitric oxide concentration and maximum airway nitric oxide flux and their correlation with height were studied. The correlation among the fraction of exhaled NO at 50 ml/s (FENO50), CANO, JawNO, forced expiratory volume in 1 second (FEV1) and the CAN questionnaire was measured and the degree of agreement regarding asthma control assessment was studied using Cohen's kappa. RESULTS: We studied 162 children; 49 healthy (group 1), 23 asthmatic participants without treatment (group 2) and 80 asthmatic patients treated with inhaled corticosteroids (group 3). CANO (ppb) was 2.2 (0.1-4.5), 3 (0.2-9.2) and 2.45 (0.1-24), respectively. JawNO (pl/s) was 516 (98.3-1470), 2356.67 (120-6110) and 1426 (156-11805), respectively. There was a strong association (r=0.97) between FENO50 and JawNO and the degree of agreement was very good in group 2 and was good in group 3. There was no agreement or only slight agreement between the measures used to monitor asthma control (FEV1, CAN questionnaire, CANO and JawNO). CONCLUSIONS: The results for CANO and JawNO in controls were similar to those found in other reports. There was no agreement or only slight agreement among the three measure instruments analyzed to assess asthma control. In our sample, no additional information was provided by CANO and JawNO.

Evaluating acceptance and user experience of a guideline-based clinical decision support system execution platform.

This study aims to determine what the initial disposition of physicians towards the use of Clinical Decision Support Systems (CDSS) based on Computerised Clinical Guidelines and Protocols (CCGP) is; and whether their prolonged utilisation has a positive effect on their intention to adopt them in the future. For a period of 3 months, 8 volunteer paediatricians monitored each up to 10 asthmatic patients using two CCGPs deployed in the-GuidesMed CDSS. A Technology Acceptance Model (TAM) questionnaire was supplied to them before and after using the system. Results from both questionnaires are analysed searching for significant improvements in opinion between them. An additional survey was performed to analyse the usability of the system. It was found that initial disposition of physicians towards e-GuidesMed is good. Improvement between the pre and post iterations of the TAM questionnaire has been found to be statistically significant. Nonetheless, slightly lower values in the Compatibility and Habit variables show that participants perceive possible difficulties to integrate e-GuidesMed into their daily routine. The variable Facilitators shows the highest correlation with the Intention to Use. Usability of the system has also been rated very high and, in this regard, no fundamental flaw has been detected. Initial views towards e-GuidesMed are positive, and become reinforced after continued utilisation of the system. In order to achieve an effective implementation, it becomes essential to facilitate conditions to integrate the system into the physician's daily routine.

Dynamics of Streptococcus pneumoniae serotypes causing acute otitis media isolated from children with spontaneous middle-ear drainage over a 12-year period (1999-2010) in a region of northern Spain.

The aim of this study was to determine the serotype and clonal distribution of pneumococci causing acute otitis media (AOM) and their relationship with recurrences and mixed infections with other microorganisms under the influence of the 7-valent pneumococcal conjugate vaccine (PCV7). To do this, all pneumococcal isolates collected from the spontaneous middle-ear drainage of children <5 years old diagnosed of AOM by their pediatrician or their general practitioner from 1999 to 2010 were phenotypically characterized and the most frequent serotypes were genotyped. In the 12-year study, 818 episodes of pneumococcal AOM were detected, mostly (70.5%) in children younger than 2 years old. In 262 episodes (32%), the pneumococci were isolated with another bacterium, mainly (n=214) Haemophilus influenzae. Mixed infections were similar in children under or over 2 years old. The most frequent serotypes were 19A (n=227, 27.8%), 3 (n=92, 11.2%) and 19F (n=74, 9%). Serotypes included in the PCV7 sharply decreased from 62.4% in the pre-vaccination (1999-2001) to 2.2% in the late post-vaccination period (2008-2010). Serotype diversity steadily increased after the introduction of the PCV7 but decreased from 2008-2010 due to the predominant role of serotype 19A isolates, mostly ST276 and ST320. The prevalence of serotype 3 doubled from 6.1% (20/326) in 1999-2004 to 14.6% (72/492) in 2005-2010. Relapses mainly occurred in male infants infected with isolates with diminished antimicrobial susceptibility. Reinfections caused by isolates with the same serotype but different genotype were frequent, highlighting the need for genetic studies to differentiate among similar strains. In conclusion, the main change in pneumococcal AOM observed after the introduction of the PCV7 was the sharp decrease in vaccine serotypes. Also notable was the high burden of serotype 19A in total pneumococcal AOM before and especially after the introduction of the PCV7, as well as in relapses and reinfections.

Young infants with recurrent wheezing and positive asthma predictive index have higher levels of exhaled nitric oxide.

OBJECTIVE: The aim of this post hoc analysis was to establish the relationship between FE(NO) levels and the asthma predictive index (API) among infants with recurrent wheezing. METHODS: Infants with recurrent wheezing (three or more episodes) were recruited consecutively and online FE(NO) tests at tidal breathing with multiple breaths were performed. RESULTS: Twenty-seven (84%) out of 32 infants (median age of 12 months) who met the inclusion criteria for this post hoc analysis, successfully performed the FE(NO) determinations. Eighteen (66%) infants were classified with positive stringent API. FE(NO) levels were significantly higher among patients with positive API than those with negative (median [IQR] of 12.3 [14.8] ppb vs. 4.1 [7.9] ppb, respectively, p = .016). Furthermore, FE(NO) and positive API had a significant correlation (Spearman's rho, ρ = 0.4741, p = .0125). After logistic regression analysis including FE(NO) levels, gender, age, and use of controller therapy, FE(NO) was the only variable that was marginally related to API (OR = 1.12, 95% CI: 0.99-1.27, p = .07). CONCLUSION: Infants with recurrent wheezing who had a positive stringent API already had higher FE(NO) levels than those with a negative API. This finding needs to be corroborated in a larger prospective study.

Óxido nítrico exhalado e índice predictivo de asma en menores de dos años / Fraction of Exhaled Nitric Oxide and Asthma Predictive Index in Infants Less Than Two Years-Old

Introducción: La fracción exhalada del óxido nítrico (FENO) se considera marcador indirecto de la inflamacióneosinofílica de la vía aérea. En niños colaboradores la metodología habitual es mediante respiraciónúnica. La imposibilidad de realizarla en niños no colaboradores ha permitido desarrollar la técnica a respiracióncorriente on-line y off-line. El objetivo del estudio ha sido analizar la relación entre la FENO on-linea respiraciones múltiples y el índice predictivo de asma (IPA) en niños menores de dos años.Material y métodos: Estudio observacional y transversal en una muestra consecutiva de niños y niñas entredos meses y dos años de edad, durante un período de 4 meses. Se determinó la FENO postprandial onlinea respiración corriente con respiraciones múltiples y flujo espiratorio entre 40 y 60 ml/s, medianteanalizador de quimioluminiscencia estacionario (CLD 88 sp). Variables cuantitativas: edad, peso, IgE,eosinofilia, FENO, flujo espiratorio. Variables cualitativas: sexo, dermatitis atópica, rinitis alérgica, alergiaalimentaria y medicamentosa, antecedentes familiares de asma y atopia, diagnóstico y tratamiento. Seha analizado la asociación entre IPA y FENO mediante test exacto de Fisher y t de Student y el grado deacuerdo entre IPA y FENO mediante Kappa de Cohen. Se ha estudiado la relación entre eosinofilia, IgE,dermatitis atópica y FENO (test exacto de Fisher y t de Student).Resultados: Cohorte constituida por 38 pacientes. Realizaron las determinaciones con éxito 32 (84,21%)casos. Edad media 10,9±5,06 meses. Los casos con IPA positivo tenían valores de FENO significativamentesuperiores a los IPA negativos con grado de acuerdo entre IPA y FENO de 0,71.Conclusiones: Existe asociación significativa y un buen grado de acuerdo entre la FENO a respiracióncorriente online y el IPA(AU)

Introduction: The fraction of exhaled nitric oxide (FENO) is considered as an indirect marker of eosinophilicinflammation of the airway. In collaborating children the usual method is by a single breath. Theimpossibility of performing this in non-collaborating children has led to the development of the onlineand offline tidal breathing technique. The objective of the study has been to analyse the relationshipbetween the multiple breaths online FENO and the asthma predictive index (API) in children less than 2years-old.Material and methods: An observational and cross-sectional study on a consecutive sample of boys andgirls between 2 months and 2 years of age, over a period of 4 months. The post-prandial multiple breathsonline FENO and flow spirometry between 40 and 60 ml/s, using a stationary chemiluminescence analyser(CLD 88 sp). The quantitative variables were: age, weight, IgE, eosinophilia, FENO, flow spirometry. Thequalitative variables were: gender, atopic dermatitis, allergic rhinitis, food and medical allergies, familyhistory of asthma and atopy, diagnosis and treatment. The relationship between API and FENO was analysedusing the exact Fisher and Student t tests and the level of agreement between API and FENO usingCohen’s Kappa. The relationship between eosinophilia, IgE, atopic dermatitis and FENO was also studied(exact Fisher and Student t tests). Results: The cohort consisted of 38 patients. The determinations were successfully carried out on 32(84.21) of the cases. The mean age was 10.9±5.06 months. The cases with a positive API had significantlyhigher FENO values than those with a negative API, with a level of agreement between API and FENO of0.71.Conclusions: There is a significant relationship and a good level of agreement between the online tidalbreathing FENO and the API(AU)

Fraction of exhaled nitric oxide and asthma predictive index in infants less than two years-old.

INTRODUCTION: The fraction of exhaled nitric oxide (FE(NO)) is considered as an indirect marker of eosinophilic inflammation of the airway. In collaborating children the usual method is by a single breath. The impossibility of performing this in non-collaborating children has led to the development of the online and offline tidal breathing technique. The objective of the study has been to analyse the relationship between the multiple breaths online FE(NO) and the asthma predictive index (API) in children less than 2 years-old. MATERIAL AND METHODS: An observational and cross-sectional study on a consecutive sample of boys and girls between 2 months and 2 years of age, over a period of 4 months. The post-prandial multiple breaths online FE(NO) and flow spirometry between 40 and 60 ml/s, using a stationary chemiluminescence analyser (CLD 88 sp). The quantitative variables were: age, weight, IgE, eosinophilia, FE(NO), flow spirometry. The qualitative variables were: gender, atopic dermatitis, allergic rhinitis, food and medical allergies, family history of asthma and atopy, diagnosis and treatment. The relationship between API and FE(NO) was analysed using the exact Fisher and Student t tests and the level of agreement between API and FE(NO) using Cohen's Kappa. The relationship between eosinophilia, IgE, atopic dermatitis and FE(NO) was also studied (exact Fisher and Student t tests). RESULTS: The cohort consisted of 38 patients. The determinations were successfully carried out on 32 (84.21) of the cases. The mean age was 10.9±5.06 months. The cases with a positive API had significantly higher FE(NO) values than those with a negative API, with a level of agreement between API and FE(NO) of 0.71. CONCLUSIONS: There is a significant relationship and a good level of agreement between the online tidal breathing FE(NO) and the API.

Reliability and validity of the Spanish version of the TAPQOL: a health-related quality of life (HRQOL) instrument for 1- to 5-year-old children.

OBJECTIVES: To evaluate the reliability, and construct validity of the Spanish version of the TNO-AZL preschool children quality of life (TAPQOL). METHODS: A consecutive sample of children (3 months to 5 years old) was recruited from primary care centers and two teaching hospitals in Spain. The TAPQOL and a set of questions related to their child's health status were administered to parents. Clinical diagnoses were collected from clinical records. Principal component analysis (PCA) with varimax rotation was used to analyze the instrument's structure. Effect size (ES) and analysis of variance (ANOVA) were used to analyze differences between subgroups known to be in poor health compared to the healthy subgroup. RESULTS: A total of 228 children participated in the study (response rate=95%). Ten of the 12 scales showed more than 30% ceiling effect. All dimensions except one had Cronbach's alpha coefficients greater than 0.7. PCA explained 75% of the variance. Healthy children in general had better scores than the other subgroups. Children at risk of poor health outcomes and those with respiratory problems scored lower in several scales than the healthy subgroup. CONCLUSIONS: Although the Spanish TAPQOL shows a non-negligible ceiling effect, it seems to be a reliable and valid instrument for Spanish infants and toddlers, and with similar psychometric characteristics to the original version. Future studies should try to improve questionnaire's structure and assess its sensitivity to change.