O presente estudo avaliou o sistema oculomotor medido por movimentos oculares em bebês com diagnóstico de Displasia Broncopulmonar (DBP). Bebês com idade gestacional 37 semanas, dependentes de oxigênio em concentrações acima de 21% por mais de 28 dias foram incluídos no grupo DBP, bebês nascidos a Termo (idade gestacional > 37 semanas), não internados foram incluídos no grupo nascido a termo e bebês prematuros (idade gestacional < 37 semanas), que permaneceram internados e que não fizeram uso de oxigênio por mais de 10 dias foram incluídos no grupo prematuro. Os bebês dos três grupos tinham exame oftalmológico de biomicroscopia e de fundo de olho com resultados normais. Foram excluídos do estudo, bebês em uso de oxigênio sob ventilação mecânica e/ou drogas vasoativas, com diagnóstico de hemorragia intracraniana, retinopatia da prematuridade e malformações motoras e/ou neurológicas congênitas ou adquiridas identificadas no exame neonatal ou durante a estadia no berçário. Todos os bebês realizaram uma única avaliação binocular. As avaliações foram realizadas com os bebês sentados confortavelmente e eram compostas pela avaliação de quatro movimentos oculares: sacadas (SAC), perseguição lenta (PL), reflexo vestíbulo-ocular (RVO) e nistagmo optocinéticos (NOC). Os movimentos oculares foram transcritos em variável categórica (presente ou ausente) e para análise estatística foram feitas comparações entre o grupo DBP, grupo nascido a termo e grupo prematuro (Teste Cochran Q), para garantir a confiabilidade dos resultados apresentados durante a avaliação, 28% da amostra foi avaliada por três observadores e um teste de aderência X2 foi utilizado para medir a confiabilidade entre os três observadores. Durante o estudo foram avaliados 109 bebês, 107 foram incluídos no estudo, dois bebês, com IG < 37 semanas, foram excluídos por usarem oxigênio por um tempo igual há 15 dias. Dos 107 bebês avaliados, 23 foram inclusos no grupo DBP, 47 no grupo nascido a termo e 37 no grupo prematuro. Os bebês do grupo DBP tiveram IG média de 32 semanas ± 3 semanas, APGAR 1° minuto 6 ± 1, 5° minuto 8 ± 2, 37 dias em oxigênio ± 10 dias, na quantidade média de 2 L/min ± 0,5 L/min. O peso de nascimento, idade gestacional, APGAR NO 1° e 5° minutos do grupo nascido a termo, DBP e Prematuro diferem significativamente entre si (Teste Kruskal-Wallis p = 0.0000, 0.0000, 0.0000, 0.0013 e 0.0001, respectivamente). O grupo nascido a termo apresentou maiores valores quando comparado ao grupo DBP e prematuro. Bebês com DBP manifestam ausência de três dos quatro tipos de movimentos oculares medidos quando comparado com o grupo nascido a termo e prematuro (Teste Q Cochran onde Q > 2 e p, < 0,05) / This study evaluated the oculomotor system measured by eye movements in infants diagnosed with bronchopulmonary dysplasia (BPD). Infants 37 weeks gestational age, oxygen-dependent at concentrations above 21% for more than 28 days were included in the BPD group, term infants (gestational age > 37 weeks), not hospitalized were included in term groups and preterm infants (gestational age < 37 weeks), who remained hospitalized and did not use oxygen for more than 10 days were included in the premature group. The three groups of babies had eye examination and biomicroscopy of the fundus with normal results. Excluded from the study, babies on oxygen in mechanical ventilation and/ or vasoactive drugs; with a diagnosis of intracranial hemorrhage, retinopathy of prematurity, motor and/or neurological congenital or acquired malformations identified in neonatal or during the stay in the nursery. All infants made a single binocular assessment. The evaluations were conducted with babies seated comfortably and were composed by the evaluation of four eye movements: saccades (SAC), slow pursuit (PL), vestibuloocular reflex (VOR) and optokinetic nystagmus (NOC). Eye movements were transcribed into a categorical variable (present or absent) and statistical analysis were made between BPD group, term group and premature group (Cochran Q test) to ensure reliable of the results presented during the evaluation, 28 % of the sample was evaluated by three observers and an adherence X2 test was used to measure the reliable between three observers. During the study, 109 infants were evaluated, 107 were included in the study, two infants with GA < 37 weeks, were excluded by using oxygen for a time equal to 15 days. Of the 107 infants evaluated, 23 were included in the BPD group, 47 in the term group and 37 in the premature group. Babies in the BPD group had GA of 32 weeks ± 3 weeks, APGAR 1st minute 6 ± 1, 5th minutes 8 ± 2, 37 days ± 10 days in oxygen, in the median amount of 2 L / min ± 0.5 L / min. Birth weight, gestational age, APGAR score at 1st and 5th minutes from the term group, DBP and Premature differ significantly (Kruskal-Wallis test p = 0.0000, 0.0000, 0.0013 and 0.0001, respectively). The term group had higher values when compared to the BPD and premature. Babies with BPD manifest absence of three of the four types of eye movements measured when compared with the term group and preterm (Cochran Q test where Q > 2 and p < 0.05)

Orientadores: José Dirceu Ribeiro, Adyléia Aparecida Dalbo Contrera Toro / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-25T22:13:33Z (GMT). No. of bitstreams: 1 Goncalves_EmiliadaSilva_M.pdf: 2675910 bytes, checksum: 6f50e6654757e970ee9c23e71274eff4 (MD5) Previous issue date: 2014 / Resumo: Objetivo: Determinar e comparar a prevalência e fatores de risco para asma em escolares e adolescentes que nasceram com muito baixo peso(RNMBP), com e sem displasia broncopulmonar(DBP). Métodos: Estudo comparativo, observacional, de corte transversal com componente analítico. Aplicou-se aos pais, o questionário do International Study of Asthma and Allergies in Childhood(ISAAC) e aos sujeitos o teste cutâneo de hipersensibilidade imediata(TCHI). Resultados: De 366 RNMBP, nascidos entre 2000 a 2004, foram incluídos no estudo 54 crianças e adolescentes, 33 masculinos(61,1%)(9,9±0,92 anos). Não houve diferença estatística para peso de nascimento entre os gêneros(p=0,423). Caucasóides: 47/54(87%). A idade na avaliação (DBP: 9,5+085; sem DBP: 10,1+0,86 anos) e o peso de nascimento (DBP: 916,7±251,2; sem DBP: 1171,3±190,5gramas) foram menores no grupo com DBP quando comparado ao grupo sem DBP(p<0,05). A prevalência de asma entre os RNMBP foi 17/54(31,5%), sendo no grupo com DBP de 6/18(33,3%) (IC95%= 13,3-59,0) e no grupo sem DBP de 11/36(30,6%) (IC95%= 16,3-48,1). Não houve associação entre DBP e gravidade da asma e entre DBP e número de pneumonias(p>0,05). Nos fatores de risco para a asma, houve associação com o uso de cobertor de lã no primeiro ano de vida(p=0,026). O TCHI foi positivo em 13/17(76,5%) e 23/37(62,2%) nos grupos com e sem asma, respectivamente. Conclusão: Os RNMBP avaliados entre sete e 12 anos de idade, com e sem DBP, tiveram prevalência elevada de asma, porém sem diferença estatística entre os grupos. Os fatores de risco para asma não foram estatisticamente diferentes entre os grupos estudados / Abstract: Objective: To determine and compare the prevalence and risk factors for asthma in infants, children and adolescents born with very low birth weight(VLBW) with and without bronchopulmonary dysplasia(BPD) . Methods: comparative, observational, cross-sectional with an analytical component. Applied to caregivers, the questionnaire of the International Study of Asthma and Allergies in Childhood(ISAAC) and for the subjects the immediate hypersensitivity skin test(HST). Results: Of 366 VLBW infants born between 2000 and 2004 were included in the study 54 children and adolescents, 33 male(61.1%)(9.9±0.92 years). There was no statistical difference in birth weight between genders(p=0.423). Caucasoid:47/54(87%). The age at evaluation(BPD:9.5+085, no DBP: 10.1+0.86 years) and birth weight (DBP: 916.7±251.2 ; no DBP: 1171.3±190.5grams) were lower in the BPD group compared to the group no BPD(p<0.05). The prevalence of asthma among VLBW infants was 17/54(31.5%), with the BPD group of 6/18(33.3%) (95%CI= 13.3 to 59.0) in the group without BPD 11/36 (30.6%)(95%CI= 16.3 to 48.1). There was no association between BPD and asthma severity and between BPD and number of pneumonia(p>0.05). In risk factors for asthma was associated with the use of woolen blanket in the first year of life(p=0.026). The skin prick test was positive in 13/17(76.5%) and 23/37(62.2%) in patients with and without asthma, respectively. Conclusions: VLBW infants evaluated between seven and 12 years old, with and without BPD, had higher prevalence of asthma, but without significant differences between groups. Risk factors for asthma were not statistically different between groups / Mestrado / Saude da Criança e do Adolescente / Mestra em Ciências

Diploma thesis "Interaction in multisystemic problems of bronchopulmonary dysplasia - effects of physiotherapy upon lung functions of immature infants" deals with relevant questions about care of immature newborns both during hospitalization at NICU and after discharge, inclusive of examination at Center for comprehensive care for risk newborns. Especially deals with possibilities of physiotherapy of newborns with bronchopulmonary dysplasia pathology and demonstrates the necessity of tight cooperation among physiotherapists, nurses and doctors during daily care of these children. Powered by TCPDF (www.tcpdf.org)

Introduction: Infants with Bronchopulmonary Dysplasia (BPD) are at higher risk of developing severe RSV Bronchiolitis requiring hospitalisation. Palivizumab Immunoprophylaxis (PIP) was shown to reduce the severity of illness and hence the need for hospitalisation. Currently PIP is recommended for all infants with BPD, but there is little evidence on which infants with BPD would most benefit from PIP. Aim: This study aims to identify the clinical benefit of administering PIP to infants with BPD of different severities and to determine which infants would benefit most from PIP. In order to achieve this, the study also identifies the incidence of BPD, categorised into mild, moderate and severe in infants, in the Greater Manchester Region (GMR).Methods: This is a multi-centre, prospective, observational cohort study, involving 11 hospitals across GMR. Patients were recruited over 2 years, from 1st April 2009 to 31st March 2011. The infants with BPD were recruited and further categorised in various severities, based on Jobe’s BPD classification [Jobe et al 2001]. Patients were followed up for a minimum of one year. Results: The incidence of BPD in the GMR was 5.9 infants per 1000 live births. On categorisation by level of severity, the study found 31% of these to have mild BPD, 39% moderate and 30% severe BPD. Around 60% of infants received PIP in our cohort: one third of mild group, two thirds of moderate and three quarters of severe BPD. The overall proportion of hospitalisation for all the respiratory illnesses in infants with BPD was 44%. The overall incidence of hospitalization secondary to RSV infection was 7.6% of the cohort, and 14.8% due to other respiratory viruses. PIP was most beneficial in infants with moderate BPD (p = 0.016). Infants hospitalised with RSV infection required more admissions to HDU, required a longer duration of supplemental oxygen as well as a longer hospital stay compared to infants hospitalised due to other respiratory viruses and all other respiratory illnesses. Conclusion: This is the first study identifying the incidence of BPD in the GMR, which was lower than expected based on estimates from the JCVI. Both, the distribution of BPD into the various severity categories, as well as the requirement of hospital admission secondary to respiratory illness, were in keeping with published evidence from the USA and UK. PIP practices across North West of England were varied and not compliant with JCVI guidelines. Infants with moderate BPD showed the largest benefit from receiving PIP. This is a novel finding that highlights the need for further research, to determine whether a subgroup of infants might benefit from PIP.

Preterm birth (<37 weeks) is the world’s principal cause of death of children <5 years of age. Bronchopulmonary dysplasia (BPD) is the most common complication of preterm birth. BPD is characterized by an arrest in alveolar and vascular development within the lung. It is a multifactorial disease, caused by a combination of supplemental oxygen, mechanical ventilation, and inflammation. BPD is also an independent risk factor for abnormal neurodevelopment. The link between BPD and abnormal neurodevelopment is poorly understood and there are currently no effective cures for these complications. We hypothesized that a crucial cell population for brain development, i.e., the neural progenitor cell (NPC) is functionally impaired in BPD and that this impairment is associated with abnormal neurodevelopment. Based on our previous findings, we also predicted that human umbilical cord-mesenchymal stromal cell (UC-MSC) extracellular vesicles (EVs), could mitigate both the lung and brain injuries in experimental BPD. We utilized several animal models of BPD, across multiple species, to determine the effects of hyperoxia, mechanical ventilation, and inflammation on the developing lungs and brain. We also utilized UC- MSC therapy to mitigate these injuries. We discovered that hyperoxia exposure damages the developing lungs as well as the brain, leading to cerebrovascular and NPC impairments, as well as reduced neurogenesis. These impairments were associated with neurobehavioural deficits in adulthood. Furthermore, we found that inflammation in combination with mechanical ventilation and hyperoxia also impairs NPC function. Importantly, we demonstrated that UC-MSC EVs can reduce inflammation, improve vascular growth, restore lung growth, and mitigate impairments in NPC self-renewal. This work highlights novel mechanisms of BPD-associated abnormal neurodevelopment and offers potential regenerative medicine therapies to alleviate these outcomes for this vulnerable population.

京都大学 / 新制・論文博士 / 博士(医学) / 乙第13580号 / 論医博第2302号 / 新制||医||1069(附属図書館) / (主査)教授 平井 豊博, 教授 江木 盛時, 教授 齋藤 潤 / 学位規則第4条第2項該当 / Doctor of Medical Science / Kyoto University / DFAM

No description available.

Bronchopulmonary dysplasia (BPD) is a chronic neonatal lung injury (CNLI) affecting infants of < 32 weeks gestation, which has a significant associated morbidity and mortality. The hallmarks of BPD as seen in the current era are arrested alveologenesis and parenchymal thickening. Those most severely affected may develop pulmonary hypertension which worsens the prognosis. No effective preventive therapy exists. Generation of damaging reactive oxygen species is implicated in its development. The more recently recognized reactive nitrogen species may also contribute to this disease. Thus, there is considerable interest in preventive antioxidant therapies, but results to date have not been promising. Newborn rats, exposed to 60% O2 for 14 days, develop a parenchymal injury and pulmonary hypertension that resembles the morphological features of human BPD. Previous studies have shown that following exposure to 60% O2, a pulmonary influx of neutrophils is followed by that of macrophages. Inhibiting the influx of neutrophils prevents the generation of reactive oxygen species, while simultaneously enhancing postnatal lung growth. Other interventions have shown that development of pulmonary hypertension is dependent upon increases in both 8-isoprostane and its downstream regulator of vascular tone, endothelin-1. Gentler ventilation strategies, incorporated to minimize induction of stretch-mediated pro-inflammatory cytokines, have shown benefits of permissive hypercapnia in adult lung injury. Multicentre clinical trials of permissive hypercapnia in neonates have not shown benefit. Therapeutic hypercapnia has been demonstrated to have a protective effect of PaCO2 in both acute studies of ventilator-induced and ischemia-reperfusion injuries in animal models. In the studies reported herein, therapeutic hypercapnia was found to completely protect against CNLI and attenuate 60% O2-induced macrophage-derived protein nitration. The likely nitrating agent was macrophage-derived peroxynitrite. The critical role of peroxynitrite, in the development of chronic neonatal lung injury in this model, was confirmed using a peroxynitrite decomposition catalyst. This protected against the impairments of alveolarization and of pulmonary vascularization induced by 60% O2. These results suggest a more significant role for reactive nitrogen species than previously recognized. Finally, preliminary evidence is presented supporting a role for neutrophil-derived elastase in initiating the macrophage influx in the lungs, required for peroxynitrite generation, during 60% O2-mediated injury.

No description available.

Bronchopulmonary dysplasia (BPD) is a chronic neonatal lung injury (CNLI) affecting infants of < 32 weeks gestation, which has a significant associated morbidity and mortality. The hallmarks of BPD as seen in the current era are arrested alveologenesis and parenchymal thickening. Those most severely affected may develop pulmonary hypertension which worsens the prognosis. No effective preventive therapy exists. Generation of damaging reactive oxygen species is implicated in its development. The more recently recognized reactive nitrogen species may also contribute to this disease. Thus, there is considerable interest in preventive antioxidant therapies, but results to date have not been promising. Newborn rats, exposed to 60% O2 for 14 days, develop a parenchymal injury and pulmonary hypertension that resembles the morphological features of human BPD. Previous studies have shown that following exposure to 60% O2, a pulmonary influx of neutrophils is followed by that of macrophages. Inhibiting the influx of neutrophils prevents the generation of reactive oxygen species, while simultaneously enhancing postnatal lung growth. Other interventions have shown that development of pulmonary hypertension is dependent upon increases in both 8-isoprostane and its downstream regulator of vascular tone, endothelin-1. Gentler ventilation strategies, incorporated to minimize induction of stretch-mediated pro-inflammatory cytokines, have shown benefits of permissive hypercapnia in adult lung injury. Multicentre clinical trials of permissive hypercapnia in neonates have not shown benefit. Therapeutic hypercapnia has been demonstrated to have a protective effect of PaCO2 in both acute studies of ventilator-induced and ischemia-reperfusion injuries in animal models. In the studies reported herein, therapeutic hypercapnia was found to completely protect against CNLI and attenuate 60% O2-induced macrophage-derived protein nitration. The likely nitrating agent was macrophage-derived peroxynitrite. The critical role of peroxynitrite, in the development of chronic neonatal lung injury in this model, was confirmed using a peroxynitrite decomposition catalyst. This protected against the impairments of alveolarization and of pulmonary vascularization induced by 60% O2. These results suggest a more significant role for reactive nitrogen species than previously recognized. Finally, preliminary evidence is presented supporting a role for neutrophil-derived elastase in initiating the macrophage influx in the lungs, required for peroxynitrite generation, during 60% O2-mediated injury.