Antibiotic Utilization in Hospitalized Children with Bronchiolitis: A Prospective Study Investigating Clinical and Epidemiological Characteristics at a Secondary Hospital in Madrid (2004-2022).

Bronchiolitis is a viral respiratory infection, with respiratory syncytial virus (RSV) being the most frequent agent, requiring hospitalization in 1% of affected children. However, there continues to be a noteworthy incidence of antibiotic prescription in this setting, further exacerbating the global issue of antibiotic resistance. This study, conducted at Severo Ochoa Hospital in Madrid, Spain, focused on antibiotic usage in children under 2 years of age who were hospitalized for bronchiolitis between 2004 and 2022. In that time, 5438 children were admitted with acute respiratory infection, and 1715 infants (31.5%) with acute bronchiolitis were included. In total, 1470 (87%) had a positive viral identification (66% RSV, 32% HRV). Initially, antibiotics were prescribed to 13.4% of infants, but this percentage decreased to 7% during the COVID-19 pandemic thanks to adherence to guidelines and the implementation of rapid and precise viral diagnostic methods in the hospital. HBoV- and HAdV-infected children and those with viral coinfections were more likely to receive antibiotics in the univariate analysis. A multivariate logistic regression analysis revealed a statistically independent association between antibiotic prescription and fever > 38 °C (p < 0.001), abnormal chest-X ray (p < 0.001), ICU admission (p = 0.015), and serum CRP (p < 0.001). In conclusion, following guidelines and the availability of rapid and reliable viral diagnostic methods dramatically reduces the unnecessary use of antibiotics in infants with severe bronchiolitis.

Nasal TSLP and periostin in infants with severe bronchiolitis and risk of asthma at 4 years of age.

BACKGROUND: Severe bronchiolitis is often associated with subsequent respiratory morbidity, mainly recurrent wheezing and asthma. However, the underlying immune mechanisms remain unclear. The main goal of this study was to investigate the association of nasal detection of periostin and thymic stromal lymphopoietin (TSLP) during severe bronchiolitis with the development of asthma at 4 years of age. METHODS: Observational, longitudinal, post-bronchiolitis, hospital-based, follow-up study. Children hospitalized for bronchiolitis between October/2013 and July/2017, currently aged 4 years, included in a previous study to investigate the nasal airway secretion of TSLP and periostin during bronchiolitis, were included. Parents were contacted by telephone, and were invited to a clinical interview based on a structured questionnaire to obtain information on the respiratory evolution. The ISAAC questionnaire for asthma symptoms for 6-7-year-old children, was also employed. RESULTS: A total of 248 children were included (median age 4.4 years). The mean age at admission for bronchiolitis was 3.1 (IQR: 1.5-6.5) months. Overall, 21% had ever been diagnosed with asthma and 37% had wheezed in the last 12 months. Measurable nasal TSLP was detected at admission in 27(11%) cases and periostin in 157(63%). The detection of nasal TSLP was associated with the subsequent prescription of maintenance asthma treatment (p = 0.04), montelukast (p = 0.01), and the combination montelukast/inhaled glucocorticosteroids (p = 0.03). Admissions for asthma tended to be more frequent in children with TSLP detection (p = 0.07). In the multivariate analysis, adjusting for potential confounders, the detection of TSLP remained independently associated with chronic asthma treatment prescription (aOR:2.724; CI 1.051-7.063, p:0.04) and with current asthma (aOR:3.41; CI 1.20-9.66, p:0.02). Nasal detection of periostin was associated with lower frequency of ever use of short-acting beta2-agonists (SABA) (p = 0.04), lower prevalence of current asthma (p = 0.02), less prescription of maintenance asthma treatment in the past 12 months (p = 0.02, respectively). In the multivariate analysis, periostin was associated with lower risk of asthma at 4 years, independently of the atopic status (aOR:0.511 CI 95% 0.284-0.918, p:0.025). CONCLUSIONS: Our results show a positive correlation between nasal TSLP detection in severe bronchiolitis and the presence of current asthma, prescription of asthma maintenance treatment and respiratory admissions up to the age of 4 years. By contrast, we found a protective association between nasal periostin detection and current asthma at 4 years, ever diagnosis of asthma, maintenance asthma treatment prescription, and respiratory admissions.

Filaggrin and cytokines in respiratory samples of preterm infants at risk for respiratory viral infection.

Respiratory viral infections (RVIs) are frequent in preterm infants possibly inducing long-term impact on respiratory morbidity. Immune response and respiratory barriers are key defense elements against viral insults in premature infants admitted to Neonatal Intensive Care Units (NICUs). Our main goals were to describe the local immune response in respiratory secretions of preterm infants with RVIs during NICU admission and to evaluate the expression and synthesis of lung barrier regulators, both in respiratory samples and in vitro models. Samples from preterm infants that went on to develop RVIs had lower filaggrin gene and protein levels at a cellular level were compared to never-infected neonates (controls). Filaggrin, MIP-1α/CCL3 and MCP-1 levels were higher in pre-infection supernatants compared to controls. Filaggrin, HIF-1α, VEGF, RANTES/CCL5, IL-17A, IL-1ß, MIP-1α and MIP-1ß/CCL5 levels were higher during and after infection. ROC curve and logistic regression analysis shows that these molecules could be used as infection risk biomarkers. Small airway epithelial cells stimulated by poly:IC presented reduced filaggrin gene expression and increased levels in supernatant. We conclude that filaggrin gene and protein dysregulation is a risk factor of RVI in newborns admitted at the NICU.

Reduced miR-146a-5p Is a Biomarker of Infant Respiratory Diseases Contributing to Immune Dysregulation in Small Airway Epithelial Cells.

Respiratory diseases such as bronchiolitis, and those with wheezing episodes, are highly important during infancy due to their potential chronicity. Immune response dysregulation is critical in perpetuating lung damage. Epigenetic modifications including microRNA (miRNA) post-transcriptional regulation are among the factors involved in alleviating inflammation. We evaluated the expression of miR-146a-5p, a previously described negative regulator of immunity, in infants with respiratory diseases, in order to study epigenetic regulation of the immune response. Nasopharyngeal aspirate (NPA) was obtained from infants with bronchiolitis (ongoing and post-disease) or with wheezing episodes in addition to healthy controls. Virus presence was determined by nested PCR, while miRNA and gene expression were studied in cells from NPAs using qPCR. Healthy small airway epithelial cells (SAECs) were used as an in vitro model. We observe a reduction in miR-146a-5p expression in infants with either of the two diseases compared to controls, suggesting the potential of this miRNA as a disease biomarker. Post-bronchiolitis, miR-146a-5p expression increases, though without reaching levels of healthy controls. MiR-146a-5p expression correlates inversely with the immune-related gene PTGS2, while its expression correlates directly with TSLP. When heathy donor SAECs are stimulated by poly:IC, we observe an increase in miR-146a-5p, with wounds having a synergistic effect. In conclusion, infants with respiratory diseases present reduced miR-146a-5p expression, possibly affecting immune dysregulation.

Lung function, allergic sensitization and asthma in school-aged children after viral-coinfection bronchiolitis.

Our main objective was to compare the lung function, the rate of allergic sensitization and the prevalence of asthma at 7-9 years in children hospitalized for bronchiolitis with viral coinfection versus single viral infection. Observational study in children with previous bronchiolitis and current age 7-9 years. Clinical data were collected. Fraction of exhaled nitric oxide (FeNO) determination, spirometry and skin prick test for common aeroallergens were performed. A total of 181 children hospitalized for bronchiolitis (40 coinfections and 141 single infections), with median age of 8.3 years (IQR:7.5-9.1) were included. Single-HRV-infections showed lower basal FEV1(%) than coinfections (p = 0.04) and lower z-score FEV1 than single-RSV-infections (p = 0.04) or coinfections (p = 0.02). Also, single-HRV-infections had lower post-bronchodilator FEV1(%) and z-score FEV1 values than coinfections (p = 0.03 and p = 0.03). Single-HRV-bronchiolitis was an independent risk factor for FEV1 < 80% (p = 0.007). FeNO value > 25 ppb was detected in 21(12.5%) cases, without differences between viral groups (p = 0.768). The prevalence of allergic sensitization was similar in coinfections (31.4%) versus single infections (38.7%), (p = 0.428). The highest frequency of allergic rhinitis was observed in single-HRV patients (p = 0.004). The respiratory morbidity at 7-9 years of coinfected patients was similar to the single-HRV ones. In contrast, the likelihood of current asthma was up to 5 times higher in RSV/HRV coinfections than in the single-RSV-infections ones (p = 0.012). The respiratory morbidity at 7-9 years of age after severe bronchiolitis is significantly higher in single-HRV or viral coinfection patients that in single-RSV ones. Single-HRV-bronchiolitis is independently associated with lower lung function at school-age.

Dynamics of Reverse Transcription-Polymerase Chain Reaction and Serologic Test Results in Children with SARS-CoV-2 Infection.

OBJECTIVES: To determine the time to reverse transcription-polymerase chain reaction (RT-PCR) negativity after the first positive RT-PCR test, factors associated with longer time to RT-PCR negativity, proportion of children seroconverting after proven severe acute respiratory syndrome coronavirus 2 infection, and factors associated with the lack of seroconversion. STUDY DESIGN: The Epidemiological Study of Coronavirus in Children of the Spanish Society of Pediatrics is a multicenter study conducted in Spanish children to assess the characteristics of coronavirus disease 2019. In a subset of patients, 3 serial RT-PCR tests on nasopharyngeal swab specimens were performed after the first RT-PCR test, and immunoglobulin G serology for severe acute respiratory syndrome coronavirus 2 antibodies was performed in the acute and follow-up (<14 and ≥14 days after diagnosis) phase. RESULTS: In total, 324 patients were included in the study. The median time to RT-PCR negativity was 17 days (IQR, 8-29 days), and 35% of patients remained positive more than 4 weeks after the first RT-PCR test. The probability of RT-PCR negativity did not differ across groups defined by sex, disease severity, immunosuppressive drugs, or clinical phenotype. Globally, 24% of children failed to seroconvert after infection. Seroconversion was associated with hospitalization, persistence of RT-PCR positivity, and days of fever. CONCLUSIONS: Time to RT-PCR negativity was long, regardless of the severity of symptoms or other patient features. This finding should be considered when interpreting RT-PCR results in a child with symptoms, especially those with mild symptoms. Seroprevalence and postimmunization studies should consider that 11 in 4 infected children fail to seroconvert.

Bronchiolitis and recurrent wheezing are distinguished by type 2 innate lymphoid cells and immune response.

BACKGROUND: Recurrent wheezing (RW) is frequently developed in infants that have suffered bronchiolitis (BCH) during first months of life, but the immune mechanism underlying is not clear. The goal was to analyze the innate immune response that characterizes BCH and RW. METHODS: Ninety-eight and seventy hospitalized infants with BCH or RW diagnosis, respectively, were included. Nasopharyngeal aspirate (NPA) was processed. Cellular pellet was employed to evaluate type 2 innate lymphoid cells (ILC2) by flow cytometry and mRNA expression assays by semi-quantitative real-time PCR (qRT-PCR). In supernatant, twenty-seven pro-inflammatory and immunomodulatory factors, as well as lipid mediators and nitrites, were evaluated by ELISA and Luminex. RESULTS: Bronchiolitis patients showed higher ILC2 percentage compared with RW (P < .05). Also, ST2+ /ILC2 percentage was higher in the BCH group than in the RW group (P < .01). TLR3, IL33, IFNG, IL10, and FLG mRNA levels were significantly increased in BCH vs RW (P < .05). In supernatant, no significant differences were reached, observing similar levels of parameters linked to vascular damage, monocyte activation, and fibroblast growth. Prostaglandin E2 and cysteinyl leukotrienes C4 were evaluated; a significant difference was only found in their ratio. CONCLUSION: Bronchiolitis is associated with elevated nasal percentage of ILC2. This cellular population could be the key element in the differential immune response between BCH and RW which share some mechanisms such us monocyte activation, vascular damage, and fibroblast repair. Lipid mediators could play a role in the evolution of the disease later in life through innate lymphoid cells.

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Asthma prevalence, lung and cardiovascular function in adolescents born preterm.

Our main objective was to study respiratory evolution and pulmonary and cardiac function in adolescents born preterm in the post-surfactant era. Observational cross-sectional study, comparing very preterm (< 32 weeks) and moderately-late preterm adolescents (≥ 32 weeks) (74 each group). We recorded respiratory symptoms, spirometry and functional echocardiogram. Very preterm adolescents required more respiratory admissions (45.9% vs. 28.4%) (p = 0.03, OR 2.1, CI95% 1.1-4.2) and had more current asthma (21.6% vs. 9.5%, p = 0.04, OR 2.3, CI95% 1.1-5.2). Preterm subjects with intrauterine growth restriction (IUGR) presented lower FEV1 (88.7 ± 13.9 vs. 95.9 ± 13.3, p = 0.027) and lower FVC (88.2 ± 13.6 vs. 95.5 ± 13.3, p = 0.025). When assessing right ventricle, very preterm showed a greater E/E' ratio (p = 0.02) and longer myocardial performance index (MPI) (p = 0.001). Adolescents with IUGR showed less shortening fraction (p = 0.016), worse E/E' ratio (p = 0.029) and longer MPI (p = 0.06). Regarding left ventricle, very preterm showed less E' wave velocity (p = 0.03), greater E/E' ratio (p = 0.005) and longer MPI (p < 0.001). Gestational age < 32 weeks is independently associated with current asthma in adolescence. Children 13-14 years old born very preterm required more respiratory admissions and had poorer diastolic and global function of both ventricles. IUGR is a risk factor for poorer lung function in preterm adolescents, regardless gestational age.

Documento de consenso sobre la neumonía adquirida en la comunidad en los niños. SENP-SEPAR-SEIP / Consensus Document on Community-Acquired Pneumonia in Children. SENP-SEPAR-SEIP

La neumonía adquirida en la comunidad (NAC) es una enfermedad prevalente en la edad pediátrica y que ofrece frecuentemente dudas tanto diagnósticas como terapéuticas. Se ha realizado un consenso entre SEPAR, SENP y SEIP, con las siguientes conclusiones: 1. La etiología depende fundamentalmente de la edad y de otros factores, como estado inmunitario, presencia de enfermedad de base o estado vacunal y no existe un marcador analítico único con una absoluta fiabilidad diagnóstica. 2. Ante la sospecha clínica de neumonía, no es imprescindible la realización de una radiografía de tórax en los niños sanos. La ecografía torácica se va imponiendo como método de seguimiento, e incluso de diagnóstico. 3. El tratamiento antibiótico empírico de elección en las formas típicas es la amoxicilina oral a una dosis de 80mg/kg/ día generalmente durante 7 días, mientras que en las atípicas en mayores de 5 años son los macrólidos. En las formas típicas graves se recomienda la combinación de cefalosporina de 3.a generación y cloxacilina (o clindamicina o vancomicina) por vía intravenosa. 4. En caso de requerir drenaje pleural, se recomienda la inserción ecoguiada de un catéter de pequeño tamaño. La administración intrapleural de fibrinolíticos (urocinasa) reduce la estancia hospitalaria en comparación con el drenaje pleural simple. 5. En el derrame pleural paraneumónico el tratamiento con antibioticoterapia junto con drenaje pleural y fibrinolíticos se asocia con una estancia hospitalaria y una tasa de complicaciones similar al tratamiento antibiótico más videotoracoscopia asistida. 6. Se recomienda la vacunación antineumocócica conjugada sistemática en menores de 5 años, ya que reduce la incidencia de NAC y de hospitalización por esta causa

Community-acquired pneumonia (CAP) is a prevalent disease among children and is frequently associated with both diagnostic and therapeutic uncertainties. Consensus has been reached between SEPAR, SENP and SEIP, and their conclusions are as follows: 1. Etiology depends mainly on age and other factors and no single analytical marker offers absolute diagnostic reliability. 2. In the event of clinical suspicion of pneumonia in a healthy child, chest X-ray is not necessary. Chest ultrasound is increasingly implemented as a follow-up method, and even as a diagnostic method. 3. The empirical antibiotic treatment of choice In typical forms of the disease is oral amoxicillin at a dose of 80mg/kg/day for 7 days, while in atypical presentations in children older than 5 years, macrolides should be selected. In severe typical forms, the combination of 3rd generation cephalosporins and cloxacillin (or clindamycin or vancomycin) administered intravenously is recommended. 4. If pleural drainage is required, ultrasound-guided insertion of a small catheter is recommended. Intrapleural administration of fibrinolytics (urokinase) reduces hospital stay compared to simple pleural drainage. 5. In parapneumonic pleural effusion, antibiotic treatment combined with pleural drainage and fibrinolytics is associated with a similar hospital stay and complication rate as antibiotic treatment plus video-assisted thoracoscopy. 6. Systematic pneumococcal conjugate vaccination is recommended in children under 5 years of age, as it reduces the incidence of CAP and hospitalization for this disease

Impact of Prematurity and Severe Viral Bronchiolitis on Asthma Development at 6-9 Years.

BACKGROUND: Premature birth is associated with increased susceptibility for viral infections and chronic airway morbidity. Preterm children, even moderate and late, may be at risk for short- and long-term respiratory morbidities. OBJECTIVE: Our main goal was to compare the burden of two conditions, severe bronchiolitis and prematurity (early and moderate-late), on asthma development at 6-9 years. PATIENTS AND METHODS: A retrospective cohort of all preterm (<37weeks gestational age) and full-term children hospitalized for bronchiolitis, with current age between 6 and 9 years, was created. A second cohort was made up of preterm children, without admission for bronchiolitis, randomly chosen from the hospital premature births database. Prevalence and risk factors for asthma were analysed. Parents completed the International Study of Asthma and Allergies in Childhood (ISAAC) Questionnaire for asthma symptoms for children 6-7 years. Lung function and aeroallergen sensitization were evaluated. RESULTS: Of the 480 selected children, 399 could be contacted and agreed to participate: 133 preterm and 114 full-term cases with admission for bronchiolitis and 146 preterm control children without admission for bronchiolitis. The frequency of current asthma at 6-9 years was higher in preterm cases (27%) compared with full-term-cases (15%) and preterm controls (14%) (p=0.04). Among hospitalized-bronchiolitis children, prematurity (p=0.04), rhinovirus infection (p=0.03), viral coinfection (p=0.04) and paternal asthma (p=0.003) were risk factors for asthma at 6-9 years. Among premature children, with and without bronchiolitis admission, the risk factors for asthma at 6-9 years were admission for bronchiolitis (p=0.03) and aeroallergen sensitisation (p=0.01). Moderate and late preterm children without admission for bronchiolitis showed similar prevalence of current asthma than full-term ones, previously admitted for bronchiolitis. CONCLUSION: Preterm birth is an important early life risk factor for asthma in childhood. The addition of other risk factors, such as severe bronchiolitis, especially by rhinovirus or viral coinfections, are associated with even higher risk for subsequent asthma.

Consensus Document on Community-Acquired Pneumonia in Children. SENP-SEPAR-SEIP. / Documento de consenso sobre la neumonía adquirida en la comunidad en los niños. SENP-SEPAR-SEIP.

Community-acquired pneumonia (CAP) is a prevalent disease among children and is frequently associated with both diagnostic and therapeutic uncertainties. Consensus has been reached between SEPAR, SENP and SEIP, and their conclusions are as follows.

Immune recovery following bronchiolitis is linked to a drop in cytokine and LTC4 levels.

BACKGROUND: Bronchiolitis is the main cause of hospitalization of children younger than 1 year; however, the immune mechanism of bronchiolitis is not completely understood. The aim of this study was to analyze the recovery of immune response after a bronchiolitis episode. METHODS: Forty-nine infants hospitalized with bronchiolitis diagnosis were enrolled. Nasopharyngeal aspirates (NPAs) were processed. Twenty-seven pro-inflammatory biomarkers linked to innate immunity, inflammation, and epithelial damage, as well as nitrites and lipid mediators, were evaluated in the NPA supernatant by ELISA (enzyme-linked immunosorbent assay) and Luminex. Also, 11 genes were analyzed in NPA cells by quantitative PCR. RESULTS: A widespread statistically significant decline of multiple pro-inflammatory parameters and cytokines were detected in the recovery period after respiratory infection: interferon-α2 (IFNα2), IFNγ, interleukin-10 (IL-10), IL-1ß, IL-8, IFN-γ-inducible protein-10, vascular endothelial growth factor, monocyte chemoattractant protein-1, macrophage inflammatory protein-1α (MIP-1α), and MIP-1ß. Supporting these results, a decreased nuclear factor-κB gene expression was observed (P = 0.0116). A significant diminution of cysteinyl leukotriene C4 (LTC4) soluble levels (P = 0.0319) and cyclooxygenase-2 (COX-2) gene expression were observed in the recovery sample. In children classified by post-bronchiolitis wheezing, LTC4 remains elevated in the NPA supernatant. CONCLUSIONS: After bronchiolitis, cytokines and biomarkers linked to innate immune response in NPA decrease significantly in the recovery period accompanied by a drop in LTC4 levels; however, this reduction was lower in infants with post-bronchiolitis wheezing.

Target-independent high-throughput sequencing methods provide evidence that already known human viral pathogens play a main role in respiratory infections with unexplained etiology.

Despite the advanced PCR-based assays available, a fraction of the pediatric respiratory infections remain unexplained every epidemic season, and there is a perception that novel viruses might be present in these specimens. We systematically collected samples from a prospective cohort of pediatric patients with respiratory infections, that returned negative results by validated molecular RT-PCR assays, and studied them with a target-independent, high-throughput sequencing-based approach. We also included a matched cohort of children with no symptoms of respiratory infection, as a contrast study population. More than fifty percent of the specimens from the group of patients with unexplained respiratory infections were resolved. However, the higher rate of detection was not due to the presence of novel viruses, but to the identification of well-known viral respiratory pathogens. Our results show that already known viral pathogens are responsible for the majority of cases that remain unexplained after the epidemic season. High-throughput sequencing approaches that use pathogen-specific probes are easier to standardize because they ensure reproducible library enrichment and sequencing. In consequence, these techniques might be desirable from a regulatory standpoint for diagnostic laboratories seeking to benefit from the many advantages of these sequencing technologies.

The role of respiratory viruses in children with humoral immunodeficiency on immunoglobulin replacement therapy.

BACKGROUND: The role of viruses in children with respiratory tract infections and humoral immunodeficiencies has hardly been studied. We have evaluated these infections in children with humoral immunodeficiencies who required immunoglobulin replacement therapy, considering their relationship with symptoms, lung function, bacterial co-infection, and outcomes. METHODS: We conducted a prospective case-control study during a 1-year period, including children with humoral immunodeficiencies receiving immunoglobulin replacement therapy. For each patient, at least one healthy family member was included. Respiratory samples for viral detection were taken every 1-3 months, and in case of respiratory tract infections. Symptoms questionnaires were filled biweekly. Spirometry and sputum culture were performed in every episode. RESULTS: Sixty-six episodes were analyzed in 14 patients (median age 12 years; IQR 7-17), identifying 18 respiratory viruses (27.3%), being rhinovirus the most frequently isolated one (12/18; 66%). Positive viral episodes were associated with clinical symptoms (89% vs 43%), more frequent antibiotic treatment (44% vs 15%) or hospital admission (22% vs 0%) than negative ones. Patients with positive viral detection showed impaired lung function, with lower FEV1 and FVC values. CONCLUSIONS: In our experience, viral respiratory tract infections can cause significant respiratory symptoms and impaired lung function, in children with HID, despite immunoglobulin replacement therapy. These patients could benefit from the monitoring of viral infections, as these may be a gateway for ongoing lung damage.

Role of viral coinfections in asthma development.

BACKGROUND: Viral respiratory infections, especially acute bronchiolitis, play a key role in the development of asthma in childhood. However, most studies have focused on respiratory syncytial virus or rhinovirus infections and none of them have compared the long-term evolution of single versus double or multiple viral infections. OBJECTIVE: Our aim was to compare the frequency of asthma development at 6-8 years in children with previous admission for bronchiolitis associated with single versus double or multiple viral infection. PATIENTS & METHODS: A cross-sectional study was performed in 244 children currently aged 6-8 years, previously admitted due to bronchiolitis between September 2008 and December 2011. A structured clinical interview and the ISAAC questionnaire for asthma symptoms for 6-7-year-old children, were answered by parents by telephone. Specimens of nasopharyngeal aspirate for virological study (polymerase chain reaction) and clinical data were prospectively taken during admission for bronchiolitis. RESULTS: Median current age at follow-up was 7.3 years (IQR: 6.7-8.1). The rate of recurrent wheezing was 82.7% in the coinfection group and 69.7% in the single-infection group, p = 0.06. The number of wheezing-related admissions was twice as high in coinfections than in single infections, p = 0.004. Regarding the ISAAC questionnaire, 30.8% of coinfections versus 15% of single infections, p = 0.01, presented "wheezing in the last 12 months", data that strongly correlate with current prevalence of asthma. "Dry cough at night" was also reported more frequently in coinfections than in single infections, p = 0.02. The strongest independent risk factors for asthma at 6-8 years of age were: age > 9 months at admission for bronchiolitis (OR: 3.484; CI95%: 1.459-8.317, p:0.005), allergic rhinitis (OR: 5.910; 95%CI: 2.622-13.318, p<0.001), and viral coinfection-bronchiolitis (OR: 3.374; CI95%: 1.542-7.386, p:0.01). CONCLUSIONS: Asthma at 6-8 years is more frequent and severe in those children previously hospitalized with viral coinfection-bronchiolitis compared with those with single infection. Allergic rhinitis and older age at admission seem also to be strong independent risk factors for asthma development in children previously hospitalised because of bronchiolitis.

Infecciones virales respiratorias en una cohorte de niños durante el primer año de vida y su papel en el desarrollo de sibilancias / Respiratory viral infections in a cohort of children during the first year of life and their role in the development of wheezing

Introducción: Las infecciones respiratorias virales que requieren hospitalización parecen conferir riesgo de desarrollar sibilancias recurrentes, pero existen pocos datos publicados en poblaciones no seleccionadas por tener factores de riesgo. Nuestro objetivo principal fue analizar si las infecciones respiratorias virales sintomáticas y asintomáticas, de diferente gravedad, durante el primer año de vida en una cohorte de recién nacidos, suponen un mayor riesgo de sibilancias recurrentes. Pacientes y métodos: Se incluyeron 302 recién nacidos. Se recogió aspirado nasofaríngeo a los niños cuando presentaron una infección respiratoria y de forma periódica en los controles de salud (2, 4, 6 y 12 meses). Se estudiaron 16 virus respiratorios mediante reacción en cadena de polimerasa (PCR). Resultados: Se analizaron 1.293 muestras (1.005 controles de salud y 288 infecciones respiratorias). El 30,8% de las muestras tomadas en los controles de salud fueron positivas, frente a un 77,8% en las infecciones respiratorias, p < 0,001 (OR: 3, IC 95%: 2,4-3,8). Un total de 239 (79%) lactantes tuvieron al menos una detección viral positiva durante el primer año de vida. El virus más frecuentemente identificado (71%) fue el rinovirus (RV). En 27 lactantes (11%) se detectaron sibilancias recurrentes durante su primer año de vida (2,9 DE: 1,2 episodios). El 58,3% de los lactantes cuya primera infección respiratoria requirió hospitalización desarrollaron sibilancias de repetición, frente al 8,6% de los niños cuya primera infección fue leve o asintomática, p < 0,001 (OR: 2,18; lC 95%: 1,05-4,5). Conclusiones: En nuestra serie, las infecciones respiratorias virales graves en los primeros meses de vida supusieron un factor de riesgo para desarrollar sibilancias recurrentes. No ocurrió lo mismo con las infecciones respiratorias leves (AU)

Introduction: It is known that infants with viral respiratory infections severe enough to require hospital admission have a high risk of developing recurrent wheezing. Few data have been published on unselected populations. The main aim of this study was to analyse symptomatic and asymptomatic respiratory viral infections during the first year of life in a cohort of infants, recruited at birth, and the development of recurrent wheezing. Patients and methods: A total of 302 newborns were recruited. A nasopharyngeal aspirate was taken when the patients had a respiratory infection, as well as in the visits for vaccination at 2, 4, 6, and 12 months. RT-nested PCR assays were performed to detect 16 viruses. Results: A total of 1,293 samples were analysed (1,005 healthy controls and 288 respiratory infections). Samples taken during routine check-ups were positive in 30.8% of cases, while those with respiratory infection were positive in 77.8%, P < .001 (OR: 3, 95% CI: 2.4-3.8). A total of 239 (79%) infants had at least 1 positive respiratory viral infection detected. The most frequent virus (71%) was rhinovirus (RV). Recurrent wheezing was found in 27 (11%) children during their first year of life (1.2 episodes, SD 2.9). Recurrent wheezing was present in 58.3% of patients admitted to hospital during their first viral infection, vs. 8.6% of infants when the first infection was mild or who had asymptomatic viral detection, P < .001 (OR: 2.18; 95% CI: 1.05-4.5). Conclusions: In our series, severe respiratory infections leading to hospitalisation in the first months of life are risk factors for developing wheezing, but not in the case of mild RV infections (AU)

Thymic stromal lymphopoietin, IL-33, and periostin in hospitalized infants with viral bronchiolitis.

Much attention has recently been focused on thymic stromal lymphopoietin (TSLP), IL-33, and periostin in allergic disease, but less is known about their role in viral bronchiolitis.The aim of the study was to investigate whether infants exhibit enhanced nasal airway secretion of TSLP, IL-33, and periostin during natural respiratory viral bronchiolitis compared to healthy controls.In total, 213 infants < 2 years of age, hospitalized with bronchiolitis from October/2013 to April/2016 were enrolled alongside 45 healthy infants. Nasopharyngeal aspirates (NPA) were screened for respiratory viruses by the polymerase chain reaction. TSLP, IL-33, and periostin were measured in NPAs. Clinical data were recorded.At least 1 virus was detected in 186 (87.3%) hospitalized infants: 149 (70%) respiratory syncytial virus (RSV); 42 (19.7%) rhinovirus (HRV); 16 (7.5%) parainfluenza virus (PIV); 9 (4.2%) adenovirus; 10 (4.7%) bocavirus; and 7 (3.3%) metapneumovirus (hMPV). Infants with bronchiolitis had higher levels of TSLP (P = .02), IL-33 (P<.001), and periostin (P = .003) than healthy controls.Detectable levels of TSLP and periostin were more frequent in virus-positive than in virus-negative patients (P = .05). TSLP and IL-33 were also more common in coinfections, mainly RSV and HRV, than in single-infections (P < .05). No patient with bronchiolitis but with negative viral detection had detectable levels of nasal TSLP or IL-33. Infants with hospital stay ≥5 days were more likely to have detectable levels of nasal TSLP and periostin after adjusting by age (P = .01).Bronchiolitis by common respiratory viruses is associated with elevated nasal levels of TSLP, IL-33, and periostin, factors known to be important in the development of Th2-response. Respiratory viruses in early life might shift immune responses toward Th2, involving asthma, and allergic diseases.