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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.
Assuntos
Asma , Bronquiolite , Infecções por Vírus Respiratório Sincicial , Criança , Pré-Escolar , Humanos , Lactente , Asma/diagnóstico , Asma/tratamento farmacológico , Asma/epidemiologia , Asma/imunologia , Bronquiolite/complicações , Bronquiolite/diagnóstico , Bronquiolite/epidemiologia , Bronquiolite/imunologia , Citocinas , Seguimentos , Infecções por Vírus Respiratório Sincicial/epidemiologia , Linfopoietina do Estroma do TimoRESUMO
Introduction: Moderate-to-late preterm infants constitute the majority within the preterm infant population. Most research on preterm infants has focused on very preterm children, often treating moderate-to-late preterm infants as similar to full-term infants. Our objective was to compare clinical, respiratory, cardio-metabolic and neurodevelopmental outcomes in adolescents aged 12-15 years born moderate and late preterm with a control group of the same age born full-term. Methods: Observational cross-sectional study, comparing moderate-to-late preterm (32-36+6 weeks' gestational age) with full-term adolescents (37-41+6 weeks' gestational age; 75 each group). Perinatal and neonatal history were collected as well as data on respiratory evolution (ISAAC questionnaire for asthma symptoms for adolescents 13-14 years), anthropometric values, learning difficulties, behavioral test (screening questionnaire for high-performance autism spectrum disorder and evaluation test for attention deficit hyperactivity disorder), skin prick test, pulmonary function test, echocardiogram and blood pressure. A blood test with metabolic profile was conducted. Results: Moderate-to-late preterm adolescents had more current asthma [p = 0.008, OR3 (95% CI 1.26-7.14)] and longer duration of combined treatments to control asthma (inhaled corticosteroids and anti-leukotrienes; p = 0.048). Forced vital capacity <80% was detected more often in moderate-to-late preterm patients (p = 0.013). When assessing right ventricle, moderate-to-late preterm adolescents showed better tricuspid annular plane systolic excursion z-score (p = 0.003), shortening fraction (p < 0.001) and E/A ratio z-score (p = 0.002). Regarding left ventricular assessment, moderate-to-late preterm group had smaller ventricle diastolic diameter (p = 0.04) and lower posterior wall z-score values (p = 0.037). They also showed a better S'wave z-score (p = 0.027), E wave (p = 0.005), E/A ratio (p = 0.003) and a higher septal myocardial performance index z-score (p = 0.025). Moderate-to-late preterm adolescents presented lower weight z-score (p = 0.039), body mass index z-score (p = 0.013), Waterlow weight index (p = 0.006) and higher undernutrition index [p = 0.04; OR 1.4 (95% CI 1-1.9)]. Although there were no differences in neurodevelopmental survey or behavioral tests. Conclusion: Our findings underscore the importance of extended follow-up for this predominant group of premature infants to identify potential respiratory, cardiac and anthropometric issues that may emerge in the future.
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Growing evidence indicates that gut and respiratory microbiota have a potential key effect on bronchiolitis, mainly caused by respiratory syncytial virus (RSV). This was a prospective study of 96 infants comparing infants with bronchiolitis (n = 57, both RSV and non-RSV associated) to a control group (n = 39). Gut (feces) and respiratory [nasopharyngeal aspirate (NPA)] microbial profiles were analyzed by 16S rRNA amplicon sequencing, and respiratory viruses were identified by PCR. Clinical data of the acute episode and follow-up during the first year after infection were recorded. Pairwise comparisons showed significant differences in the gut (R2 = 0.0639, P = 0.006) and NPA (R2 = 0.0803, P = 0.006) microbiota between cases and controls. A significantly lower gut microbial richness and an increase in the NPA microbial diversity (mainly due to an increase in Haemophilus, Streptococcus, and Neisseria) were observed in the infants with bronchiolitis, in those with the most severe symptoms, and in those who subsequently developed recurrent wheezing episodes after discharge. In NPA, the higher microbial richness differed significantly between the control group and the non-RSV bronchiolitis group (P = 0.01) and between the control group and the RSV bronchiolitis group (P = 0.001). In the gut, the richness differed significantly between the control group and the non-RSV group (P = 0.01) and between the control group and the RSV bronchiolitis group (P = 0.001), with higher diversity in the RSV group. A distinct respiratory and intestinal microbial pattern was observed in infants with bronchiolitis compared with controls. The presence of RSV was a main factor for dysbiosis. Lower gut microbial richness and increased respiratory microbial diversity were associated with respiratory morbidity during follow-up. IMPORTANCE: Both the intestinal and respiratory microbiota of children with bronchiolitis, especially those with respiratory syncytial virus infection, are altered and differ from that of healthy children. The microbiota pattern in the acute episode could identify those children who will later have other respiratory episodes in the first year of life. Preventive measures could be adopted for this group of infants.
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Bronquiolite , Microbioma Gastrointestinal , Infecções por Vírus Respiratório Sincicial , Humanos , Lactente , Bronquiolite/microbiologia , Bronquiolite/virologia , Masculino , Feminino , Estudos Prospectivos , Infecções por Vírus Respiratório Sincicial/microbiologia , Infecções por Vírus Respiratório Sincicial/virologia , RNA Ribossômico 16S/genética , Bactérias/classificação , Bactérias/isolamento & purificação , Bactérias/genética , Recém-Nascido , Fezes/microbiologia , Fezes/virologia , Microbiota , Hospitalização , Sistema Respiratório/microbiologia , Sistema Respiratório/virologia , Nasofaringe/microbiologia , Nasofaringe/virologia , Índice de Gravidade de DoençaRESUMO
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.