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1.
Int J Mol Sci ; 22(3)2021 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-33498887

RESUMO

Bronchopulmonary dysplasia (BPD) remains one of the most devastating consequences of preterm birth resulting in life-long restrictions in lung function. Distorted lung development is caused by its inflammatory response which is mainly provoked by mechanical ventilation, oxygen toxicity and bacterial infections. Dysfunction of resident lung mesenchymal stem cells (MSC) represents one key hallmark that drives BPD pathology. Despite all progress in the understanding of pathomechanisms, therapeutics to prevent or treat BPD are to date restricted to a few drugs. The limited therapeutic efficacy of established drugs can be explained by the fact that they fail to concurrently tackle the broad spectrum of disease driving mechanisms and by the huge overlap between distorted signal pathways of lung development and inflammation. The great enthusiasm about MSC based therapies as novel therapeutic for BPD arises from the capacity to inhibit inflammation while simultaneously promoting lung development and repair. Preclinical studies, mainly performed in rodents, raise hopes that there will be finally a broadly acting, efficient therapy at hand to prevent or treat BPD. Our narrative review gives a comprehensive overview on preclinical achievements, results from first early phase clinical studies and challenges to a successful translation into the clinical setting.


Assuntos
Displasia Broncopulmonar/terapia , Transplante de Células-Tronco Mesenquimais , Displasia Broncopulmonar/prevenção & controle , Humanos , Pulmão
2.
Pediatrics ; 146(2)2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32665372

RESUMO

OBJECTIVES: To determine if a home oxygen therapy (HOT) management strategy that includes analysis of recorded home oximetry (RHO) data, compared with standard monthly clinic visit assessments, reduces duration of HOT without harm in premature infants. METHODS: The RHO trial was an unmasked randomized clinical trial conducted in 9 US medical centers from November 2013 to December 2017, with follow-up to February 2019. Preterm infants with birth gestation ≤37 + 0/7 weeks, discharged on HOT, and attending their first pulmonary visit were enrolled. The intervention was an analysis of transmitted RHO between clinic visits (n = 97); the standard-care group received monthly clinic visits with in-clinic weaning attempts (n = 99). The primary outcomes were the duration of HOT and parent-reported quality of life. There were 2 prespecified secondary safety outcomes: change in weight and adverse events within 6 months of HOT discontinuation. RESULTS: Among 196 randomly assigned infants (mean birth gestational age: 26.9 weeks; SD: 2.6 weeks; 37.8% female), 166 (84.7%) completed the trial. In the RHO group, the mean time to discontinue HOT was 78.1 days (SE: 6.4), compared with 100.1 days (SE: 8.0) in the standard-care group (P = .03). The quality-of-life scores improved from baseline to 3 months after discontinuation of HOT in both groups (P = .002), but the degree of improvement did not differ significantly between groups (P = .75). CONCLUSIONS: RHO was effective in reducing the duration of HOT in premature infants. Parent quality of life improved after discontinuation. RHO allows physicians to determine which infants can be weaned and which need prolonged oxygen therapy between monthly visits.


Assuntos
Displasia Broncopulmonar/terapia , Serviços Hospitalares de Assistência Domiciliar , Oximetria , Oxigenoterapia , Peso Corporal , Feminino , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Masculino , Estudos Multicêntricos como Assunto , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto
3.
F1000Res ; 92020.
Artigo em Inglês | MEDLINE | ID: mdl-32704351

RESUMO

In the current era, the survival of extremely low-birth-weight infants has increased considerably because of new advances in technology; however, these infants often develop chronic dysfunction of the lung, which is called bronchopulmonary dysplasia (BPD). BPD remains an important cause of neonatal mortality and morbidity despite newer and gentler modes of ventilation. BPD results from the exposure of immature lungs to various antenatal and postnatal factors that lead to an impairment in lung development and aberrant growth of lung parenchyma and vasculature. However, we still struggle with a uniform definition for BPD that can help predict various short- and long-term pulmonary outcomes. With new research, our understanding of the pathobiology of this disease has evolved, and many new mechanisms of lung injury and repair are now known. By utilizing the novel 'omic' approaches in BPD, we have now identified various factors in the disease process that may act as novel therapeutic targets in the future. New investigational agents being explored for the management and prevention of BPD include mesenchymal stem cell therapy and insulin-like growth factor 1. Despite this, many questions remain unanswered and require further research to improve the outcomes of premature infants with BPD.


Assuntos
Displasia Broncopulmonar/terapia , Recém-Nascido de muito Baixo Peso , Peso ao Nascer , Feminino , Humanos , Lactente , Recém-Nascido , Fator de Crescimento Insulin-Like I , Pulmão/fisiopatologia , Células-Tronco Mesenquimais/citologia , Gravidez
4.
J Cardiovasc Magn Reson ; 22(1): 50, 2020 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-32698897

RESUMO

BACKGROUND: Bronchopulmonary dysplasia (BPD) associated with pulmonary hypertension (PH) is a significant source of morbidity and mortality in premature infants. Recent advances have allowed the use of cardiovascular magnetic resonance (CMR) in the assessment of respiratory and cardiac disease in infants with BPD. In adults and older pediatric patients, decreased CMR interventricular septal curvature correlates with increased mean pulmonary artery pressure and pulmonary vascular resistance. The current study sought to determine the relationship of CMR derived septal curvature in neonates with BPD and BPD-PH with a need for PH therapy. METHODS: Forty moderate or severe BPD and 12 mild BPD or control infants were imaged without contrast between 38 and 47 weeks post-menstrual age on a neonatal-sized, neonatal intensive care unit-sited 1.5 T CMR scanner. CMR indices including eccentricity index (CMR-EI) and septal curvature were measured and compared to BPD severity and clinical outcomes including hospital length of stay (LOS), duration of respiratory support, respiratory support level at discharge and PH therapy. RESULTS: CMR-EI was directly associated and septal curvature was inversely associated with BPD severity. In a univariate analysis, CMR-EI and septal curvature were associated with increased hospital LOS, duration of respiratory support, respiratory support at hospital discharge, and need for PH therapy. In multivariable analysis CMR-EI was associated with hospital LOS and duration of respiratory support and septal curvature was associated with respiratory support at hospital discharge. Septal curvature was the only clinical or CMR variable associated with need for PH therapy (R2 = 0.66, p = 0.0014) in multivariable analysis demonstrating improved discrimination beyond CMR-EI. CONCLUSIONS: CMR derived septal curvature correlates significantly with clinical outcomes including hospital LOS, duration of respiratory support, respiratory support level at hospital discharge, and PH therapy in neonates with BPD and BPD-PH. Further, CMR derived septal curvature demonstrated improved discrimination of need for PH therapy and respiratory support at discharge compared to clinical variables and other CMR indices, supporting septal curvature as a non-invasive marker of PH in this population with potential to guide management strategies.


Assuntos
Pressão Arterial , Displasia Broncopulmonar/diagnóstico por imagem , Hipertensão Pulmonar/diagnóstico por imagem , Imagem Cinética por Ressonância Magnética , Artéria Pulmonar/fisiopatologia , Resistência Vascular , Septo Interventricular/diagnóstico por imagem , Anti-Hipertensivos/uso terapêutico , Pressão Arterial/efeitos dos fármacos , Displasia Broncopulmonar/complicações , Displasia Broncopulmonar/fisiopatologia , Displasia Broncopulmonar/terapia , Feminino , Humanos , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/fisiopatologia , Hipertensão Pulmonar/terapia , Recém-Nascido , Tempo de Internação , Masculino , Valor Preditivo dos Testes , Artéria Pulmonar/efeitos dos fármacos , Terapia Respiratória , Estudos Retrospectivos , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento , Resistência Vascular/efeitos dos fármacos , Septo Interventricular/efeitos dos fármacos , Septo Interventricular/fisiopatologia
6.
Pediatr Pulmonol ; 55(8): 1946-1954, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32353220

RESUMO

OBJECTIVES: To review 15-year trends in respiratory care of extremely preterm infants managed in a tertiary perinatal center; to identify the factors contributing to their evolution; and to determine whether these changes had an impact on infant mortality, severe morbidity, and growth. METHODS: Retrospective cohort study of infants born at 23 to 26 weeks' gestation between 2003 and 2017. Changes in respiratory care were assessed in three 5-year periods. Logistic regression was used to examine the factors associated with prolonged duration (ie, greater than the median) of invasive mechanical ventilation (IMV), noninvasive ventilation (NIV), and overall respiratory support (ORS), and those associated with adequate weight and head circumference growth. RESULTS: Of the 396 actively treated neonates, 268 (68%) survived to discharge. Between the first and third periods, IMV duration decreased from 22 (6-37) to 4 (1-14.0) days (P < .001), that of NIV increased from 24 (14-34) to 56 (44-66) days (P < .001), and that of ORS from 50 (34-68) to 63 (52-77) days (P < .001). Study period (2003-2007 vs 2013-2017) was the main factor associated with prolonged IMV (P < .001). Use of high-flow nasal cannula was the main factor associated with prolonged NIV (P = .02) and ORS (P = .02). NIV duration was associated with adequate postnatal weight (P = .003) and head circumference (P = .03) growth. Severe morbidities in survivors, including bronchopulmonary dysplasia, and survival at hospital discharge were comparable across the study periods. CONCLUSIONS: Respiratory management was characterized by a marked reduction in IMV. NIV withdrawal protocols are necessary to limit ORS duration while respecting postnatal growth requirements.


Assuntos
Hospitalização/estatística & dados numéricos , Lactente Extremamente Prematuro/crescimento & desenvolvimento , Terapia Respiratória , Displasia Broncopulmonar/terapia , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Masculino , Estudos Retrospectivos , Fatores de Tempo
9.
Zhonghua Er Ke Za Zhi ; 58(5): 381-386, 2020 May 02.
Artigo em Chinês | MEDLINE | ID: mdl-32392953

RESUMO

Objective: To compare the clinical diagnosis and outcomes of preterm infants with bronchopulmonary dysplasia (BPD) under two different diagnostic criteria. Methods: A retrospective study was performed in 157 preterm infants who were admitted to Neonatal Intensive Care Unit of the Children's Hospital, Zhejiang University School of Medicine from January 2015 to December 2018. Enrolled infants, with gestational age <32 weeks and survived >14 days, met the 2001 National Institute of Child Health and Human Development(NICHD) definition of moderate and severe BPD or died between 14 days of postnatal age and 36 weeks owing to persistent parenchymal lung disease and respiratory failure. The severities of BPD were revaluated according to the 2018 revised definition of BPD proposed by NICHD. Characteristics and outcomes of these infants were compared with the two different diagnostic criteria with t-test, nonparametric test or Chi-square test. Results: In the 157 enrolled infants (100 males), severities of BPD were classified as moderate in 62, severe in 84 and unclassifiable in 11 according to the 2001 NICHD criteria, while grade Ⅰ in 51, Ⅱ in 29, Ⅲ in 66 and ⅢA in 11 infants respectively according to the 2018 NICHD criteria. Duration of oxygen therapy, positive pressure ventilation and endotracheal intubation in grade Ⅱinfants of 2018 criteria were much longer than that in moderate infants of 2001 criteria (80 (65, 95) vs. 65 (59, 77) d, 52 (38, 58) vs.30 (19, 48) d, 10 (2, 17) vs.4 (0, 12) d, Z=-2.995, -3.750, -2.073, all P<0.05). Mortality of moderate and severe infants in 2001 criteria was 10.3% (15/146), while mortality of BPD in 2018 criteria was 16.6% (26/157). Mortality of grade Ⅲ and ⅢA BPD in 2018 criteria was much higher than mortality of severe BPD in 2001 criteria (33.8% (26/77) vs. 17.9%(15/84), χ(2)=5.357, P<0.05). Conclusion: Definition and classification of BPD based on 2001 NICHD criteria may cause missed or unclassified cases, resulting in the underestimation of the morbidity and mortality of infants with severe BPD.


Assuntos
Displasia Broncopulmonar/diagnóstico , Displasia Broncopulmonar/terapia , Displasia Broncopulmonar/mortalidade , Feminino , Idade Gestacional , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Pulmão , Masculino , Estudos Retrospectivos , Resultado do Tratamento
10.
Am J Respir Crit Care Med ; 202(7): 1024-1031, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32459506

RESUMO

Rationale: Bronchopulmonary dysplasia is a heterogeneous lung disease characterized by regions of cysts and fibrosis, but methods for evaluating lung function are limited to whole lung rather than specific regions of interest.Objectives: Respiratory-gated, ultrashort echo time magnetic resonance imaging was used to test the hypothesis that cystic regions of the lung will exhibit a quantifiable Vt that will correlate with ventilator settings and clinical outcomes.Methods: Magnetic resonance images of 17 nonsedated, quiet-breathing infants with severe bronchopulmonary dysplasia were reconstructed into end-inspiration and end-expiration images. Cysts were identified and measured by using density threshold combined with manual identification and segmentation. Regional Vts were calculated by subtracting end-expiration from end-inspiration volumes in total lung, noncystic lung, total-cystic lung, and individual large cysts.Measurements and Main Results: Cystic lung areas averaged larger Vts than noncystic lung when normalized by volume (0.8 ml Vt/ml lung vs. 0.1 ml Vt/ml lung, P < 0.002). Cyst Vt correlates with cyst size (P = 0.012 for total lung cyst and P < 0.002 for large cysts), although there was variability between individual cyst Vt, with 22% of cysts demonstrating negative Vt. Peak inspiratory pressure positively correlated with total lung Vt (P = 0.027) and noncystic Vt (P = 0.015) but not total lung cyst Vt (P = 0.8). Inspiratory time and respiratory rate did not improve Vt of any analyzed lung region.Conclusions: Cystic lung has greater normalized Vt when compared with noncystic lung. Ventilator pressure increases noncystic lung Vt, but inspiratory time does not correlate with Vt of normal or cystic lung.


Assuntos
Displasia Broncopulmonar/diagnóstico por imagem , Cistos/diagnóstico por imagem , Imagem por Ressonância Magnética/métodos , Respiração Artificial/métodos , Volume de Ventilação Pulmonar/fisiologia , Displasia Broncopulmonar/fisiopatologia , Displasia Broncopulmonar/terapia , Cistos/fisiopatologia , Feminino , Humanos , Imageamento Tridimensional , Lactente , Lactente Extremamente Prematuro , Recém-Nascido , Masculino , Técnicas de Imagem de Sincronização Respiratória
11.
Arch Dis Child Fetal Neonatal Ed ; 105(5): 563-568, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32253200

RESUMO

Recent decades have seen the rapid progress of neonatal intensive care, and the survival rates of the most preterm infants are improving. This improvement is associated with changing patterns of morbidity and new phenotypes of bronchopulmonary dysplasia and preterm brain injury are recognised. Inflammation and immaturity are known contributors to their pathogenesis. However, a new phenomenon, the exhaustion of progenitor cells is emerging as an important factor. Current therapeutic approaches do not adequately address these new mechanisms of injury. Cell therapy, that is the use of stem and stem-like cells, with its potential to both repair and prevent injury, offers a new approach to these challenging conditions. This review will examine the rationale for cell therapy in the extremely preterm infant, the preclinical and early clinical evidence to support its use in bronchopulmonary dysplasia and preterm brain injury. Finally, it will address the challenges in translating cell therapy from the laboratory to early clinical trials.


Assuntos
Lesões Encefálicas/terapia , Displasia Broncopulmonar/terapia , Transplante de Células/métodos , Lactente Extremamente Prematuro , Doenças do Prematuro/terapia , Animais , Transplante de Células/efeitos adversos , Protocolos Clínicos , Ensaios Clínicos como Assunto , Transplante de Células-Tronco de Sangue do Cordão Umbilical/efeitos adversos , Transplante de Células-Tronco de Sangue do Cordão Umbilical/métodos , Sangue Fetal , Humanos , Recém-Nascido , Recém-Nascido de muito Baixo Peso , Terapia Intensiva Neonatal/métodos , Transplante de Células-Tronco Mesenquimais/efeitos adversos , Transplante de Células-Tronco Mesenquimais/métodos , Fatores de Tempo
12.
Pediatr Pulmonol ; 55(6): 1359-1365, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32348638

RESUMO

BACKGROUND: Roughly half of all extremely preterm infants will be diagnosed with bronchopulmonary dysplasia (BPD), and a third will be discharged on home oxygen therapy (HOT). To date, there have been no studies that have examined the relationship between respiratory medication utilization in infants with BPD on HOT. METHODS: The recorded home oximetry trial was a multicenter, randomized trial comparing two home oxygen management strategies in premature infants. Infants were enrolled at first outpatient pulmonary or neonatal intensive care unit (NICU) follow-up visit with a pulmonary component. Respiratory medication prescriptions and dosage were collected from time of enrollment through 6 months after HOT discontinuation. Patients were seen monthly while on HOT and at 1, 3, and 6 months after successful discontinuation. RESULTS: During protocol visits, 174 (89%) infants had respiratory medications documented. Respiratory medication use was higher at initial follow-up visit compared with NICU discharge and decreased at the final 6-month follow-up visit. Infants who received inhaled steroids (IS) before weaning had mean HOT duration of 138 days (range: 24-562 days); infants who received IS after weaning had shorter mean HOT duration (55 days, range: 21-264). In time-to-event analysis the no IS group and the postwean group differed significantly (χ2 1 = 8.1; P = .004). NICU clinics gave a total of 35 prescriptions to 43 patients, an average of 0.8 per patient, while the pulmonary clinics gave 837 prescriptions to 153 patients, or 5.5 per patient (P < .0001). CONCLUSION: Respiratory prescribing patterns for infants on HOT are highly variable. Utilization of IS was not associated with shorter duration of HOT.


Assuntos
Displasia Broncopulmonar/terapia , Uso de Medicamentos/estatística & dados numéricos , Oxigenoterapia , Padrões de Prática Médica , Fármacos do Sistema Respiratório/uso terapêutico , Feminino , Serviços Hospitalares de Assistência Domiciliar , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Unidades de Terapia Intensiva Neonatal , Masculino , Oximetria , Alta do Paciente
13.
Cytotherapy ; 22(4): 180-192, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32139242

RESUMO

Perinatal bronchopulmonary dysplasia (BPD) is defined as lung injury in preterm infants caused by various factors, resulting in serious respiratory dysfunction and high mortality. The administration of mesenchymal stem/stromal cells (MSCs) to treat/prevent BPD has proven to have certain therapeutic effects. However, MSCs can only weakly regulate macrophage function, which is strongly involved in the development of BPD. 7ND-MSCs are MSCs transfected with 7ND, a truncated version of CC chemokine ligand 2 (CCL2) that promotes macrophage activation, using a lentiviral vector. In the present study, we show in a BPD rat model that 7ND-MSC administration, but not MSCs alone, ameliorated the impaired alveolarization evaluated by volume density and surface area in the lung tissue, as well as pulmonary artery remodeling and pulmonary hypertension induced by BPD. In addition, 7ND-MSCs, but not MSCs alone, reduced M1 macrophages and the messenger RNA expressions of interleukin-6 and CCL2 in the lung tissue. Thus, the present study showed the treatment effect of 7ND-MSCs in a BPD rat model, which was more effective than that of MSCs alone.


Assuntos
Displasia Broncopulmonar/terapia , Quimiocina CCL2/antagonistas & inibidores , Quimiocina CCL2/genética , Hipertensão Pulmonar/terapia , Transplante de Células-Tronco Mesenquimais/métodos , Proteínas Mutantes/metabolismo , Transdução Genética , Animais , Quimiocina CCL2/metabolismo , Modelos Animais de Doenças , Feminino , Células HEK293 , Humanos , Ativação de Macrófagos/genética , Macrófagos/metabolismo , Masculino , Ratos , Ratos Wistar , Receptores CCR2/antagonistas & inibidores , Transfecção , Remodelação Vascular/genética
14.
J Pediatr ; 220: 40-48.e5, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32093927

RESUMO

OBJECTIVE: To determine associations between home oxygen use and 1-year readmissions for preterm infants with bronchopulmonary dysplasia (BPD) discharged from regional neonatal intensive care units. STUDY DESIGN: We performed a secondary analysis of the Children's Hospitals Neonatal Database, with readmission data via the Pediatric Hospital Information System and demographics using ZIP-code-linked census data. We included infants born <32 weeks of gestation with BPD, excluding those with anomalies and tracheostomies. Our primary outcome was readmission by 1 year corrected age; secondary outcomes included readmission duration, mortality, and readmission diagnosis-related group codes. A staged multivariable logistic regression was adjusted for center, clinical, and social risk factors; at each stage we included variables associated at P < .1 in bivariable analysis with home oxygen use or readmission. RESULTS: Home oxygen was used in 1906 of 3574 infants (53%) in 22 neonatal intensive care units. Readmission occurred in 34%. Earlier gestational age, male sex, gastrostomy tube, surgical necrotizing enterocolitis, lower median income, nonprivate insurance, and shorter hospital-to-home distance were associated with readmission. Home oxygen was not associated with odds of readmission (OR, 1.2; 95% CI, 0.98-1.56), readmission duration, or mortality. Readmissions for infants with home oxygen were more often coded as BPD (16% vs 4%); readmissions for infants on room air were more often gastrointestinal (29% vs 22%; P < .001). Clinical risk factors explained 72% of center variance in readmission. CONCLUSIONS: Home oxygen use is not associated with readmission for infants with BPD in regional neonatal intensive care units. Center variation in home oxygen use does not impact readmission risk. Nonrespiratory problems are important contributors to readmission risk for infants with BPD.


Assuntos
Displasia Broncopulmonar/epidemiologia , Displasia Broncopulmonar/terapia , Serviços Hospitalares de Assistência Domiciliar/estatística & dados numéricos , Recém-Nascido Prematuro , Oxigenoterapia/estatística & dados numéricos , Readmissão do Paciente/estatística & dados numéricos , Enterocolite Necrosante/epidemiologia , Feminino , Gastrostomia , Idade Gestacional , Humanos , Renda , Recém-Nascido , Seguro Saúde , Unidades de Terapia Intensiva Neonatal , Masculino , Fatores de Risco , Fatores Sexuais , Estados Unidos/epidemiologia
15.
Trials ; 21(1): 125, 2020 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-32005282

RESUMO

BACKGROUND: Bronchopulmonary dysplasia (BPD) is a complex lung pathological lesion secondary to multiple factors and one of the most common chronic lung diseases. It has a poor prognosis, especially in preterm infants. However, effective therapies for this disease are lacking. Stem-cell therapy is a promising way to improve lung injury and abnormal alveolarization, and the human umbilical cord (hUC) is a good source of mesenchymal stem cells (MSCs), which have demonstrated efficacy in other diseases. We hypothesized that intravenously administered allogeneic hUC-MSCs are safe and effective for severe BPD. METHODS: The MSC-BPD trial is a randomized, single-center, open-label, dose-escalation, phase-II trial designed to investigate the safety and efficacy of hUC-MSCs in children with severe BPD. In this study, 72 patients will be enrolled and randomly divided into two intervention groups and one control group. Patients in the intervention groups will receive a low dose of hUC-MSCs (n = 24; 2.5 million cells/kg) or a high dose of hUC-MSCs (n = 24; 5 million cells/kg) in combination with traditional supportive treatments for BPD. The patients in the control group (n = 24) will be treated with traditional supportive treatments alone without hUC-MSCs. The primary outcome measures will be cumulative duration of oxygen therapy. Follow-up assessments will be performed at 1, 3, 6, 12, and 24 months post intervention, and the key outcome during follow-up will be changes on chest radiography. Statistical analyses will evaluate the efficacy of the hUC-MSC treatment. DISCUSSION: This will be the first randomized controlled trial to evaluate the safety and efficacy of intravenously administered hUC-MSCs in children with severe BPD. Its results should provide a new evidence-based therapy for severe BPD. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT03601416. Registered on 26 July 2018.


Assuntos
Displasia Broncopulmonar/terapia , Transplante de Células-Tronco de Sangue do Cordão Umbilical/métodos , Pulmão , Células-Tronco Mesenquimais/fisiologia , Administração Intravenosa , Displasia Broncopulmonar/diagnóstico , Displasia Broncopulmonar/fisiopatologia , Ensaios Clínicos Fase II como Assunto , Feminino , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro/fisiologia , Pulmão/diagnóstico por imagem , Pulmão/fisiopatologia , Masculino , Avaliação de Resultados em Cuidados de Saúde/métodos , Oxigenoterapia/estatística & dados numéricos , Radiografia Torácica/estatística & dados numéricos , Ensaios Clínicos Controlados Aleatórios como Assunto , Índice de Gravidade de Doença
16.
BMJ Case Rep ; 13(1)2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31969395

RESUMO

Bronchopulmonary dysplasia (BPD) is occasionally associated with tracheobronchomalacia, and it is this combination that can lead to serious outcomes. The most severe cases require tracheostomies, ventilatory support and eventually even tracheal stents or surgery. Ventilation in patients with tracheomalacia is complicated without a good patient-ventilator synchrony; the neurally adjusted ventilatory assist (NAVA) mode is potentially beneficial in these cases. This case report presents a patient affected by BPD and severe tracheobronchomalacia who was tracheostomised and ventilated 24 hours a day and who suffered from episodes of airway collapse despite using the NAVA mode. It was necessary to increase the positive end-expiratory pressure to 20 cmH2O (the PEEP-20 manoeuvre) for several minutes during an episode; this allowed the trachea to remain open and allowed us to optimise the patient's ventilation. This strategy has previously been described in a patient with tracheomalacia, reducing the frequency and need for sedation in the following episodes.


Assuntos
Displasia Broncopulmonar/terapia , Respiração com Pressão Positiva , Traqueobroncomalácia/terapia , Traqueostomia , Desmame do Respirador , Humanos , Lactente
17.
Sci Rep ; 10(1): 613, 2020 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-31953419

RESUMO

We need a better risk stratification system for the increasing number of survivors of extreme prematurity suffering the most severe forms of bronchopulmonary dysplasia (BPD). However, there is still a paucity of studies providing scientific evidence to guide future updates of BPD severity definitions. Our goal was to validate a new predictive model for BPD severity that incorporates respiratory assessments beyond 36 weeks postmenstrual age (PMA). We hypothesized that this approach improves BPD risk assessment, particularly in extremely premature infants. This is a longitudinal cohort of premature infants (≤32 weeks PMA, n = 188; Washington D.C). We performed receiver operating characteristic analysis to define optimal BPD severity levels using the duration of supplementary O2 as predictor and respiratory hospitalization after discharge as outcome. Internal validation included lung X-ray imaging and phenotypical characterization of BPD severity levels. External validation was conducted in an independent longitudinal cohort of premature infants (≤36 weeks PMA, n = 130; Bogota). We found that incorporating the total number of days requiring O2 (without restricting at 36 weeks PMA) improved the prediction of respiratory outcomes according to BPD severity. In addition, we defined a new severity category (level IV) with prolonged exposure to supplemental O2 (≥120 days) that has the highest risk of respiratory hospitalizations after discharge. We confirmed these findings in our validation cohort using ambulatory determination of O2 requirements. In conclusion, a new predictive model for BPD severity that incorporates respiratory assessments beyond 36 weeks improves risk stratification and should be considered when updating current BPD severity definitions.


Assuntos
Displasia Broncopulmonar/fisiopatologia , Hospitalização/estatística & dados numéricos , Doenças do Prematuro/fisiopatologia , Oxigênio/administração & dosagem , Displasia Broncopulmonar/terapia , Feminino , Idade Gestacional , Humanos , Lactente Extremamente Prematuro , Recém-Nascido , Doenças do Prematuro/terapia , Estudos Longitudinais , Masculino , Curva ROC , Medição de Risco , Índice de Gravidade de Doença , Fatores de Tempo
18.
Curr Opin Pediatr ; 32(2): 210-215, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31833951

RESUMO

PURPOSE OF REVIEW: Clinical trials of mesenchymal stem/stromal cell (MSC) therapy for bronchopulmonary dysplasia (BPD) are underway. A thorough understanding of the preclinical work that underpins these trials is critical for neonatal practitioners to properly evaluate them. RECENT FINDINGS: Significant progress has been made in understanding that MSCs have anti-inflammatory and proangiogenic effects, and that these can be mediated by the noncellular exosome fraction of MSCs. SUMMARY: In rodent hyperoxia models of BPD, MSCs have a proangiogenic effect mediated largely by vascular endothelial growth factor and shift the balance of endogenous lung cells from a proinflammatory to a prohealing phenotype. MSC-derived exosomes can recapitulate these effects.


Assuntos
Displasia Broncopulmonar/terapia , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/imunologia , Fibrose Pulmonar/prevenção & controle , Displasia Broncopulmonar/metabolismo , Displasia Broncopulmonar/patologia , Displasia Broncopulmonar/fisiopatologia , Exossomos , Humanos , Recém-Nascido , Unidades de Terapia Intensiva Neonatal , Células-Tronco Mesenquimais/fisiologia , Fibrose Pulmonar/terapia , Resultado do Tratamento , Fator A de Crescimento do Endotélio Vascular
19.
Pediatr Neonatol ; 61(3): 272-278, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31843363

RESUMO

BACKGROUND: Bronchopulmonary dysplasia (BPD) is a common complication in very preterm infants. Despite advances in perinatal medicine, the number of BPD patients is increasing in Japan. The aim of this study was to conduct a nationwide survey of the strategies used for the prevention or treatment of BPD. METHODS: Questionnaires assessing the current strategies used to prevent or treat BPD, including neonatal resuscitation, drug therapy, and respiratory supportive care, were sent to secondary or tertiary perinatal units in 2015; responses were compared with those obtained from similar surveys in 2005 and 2010. The annual trend in incidence of BPD among the very low birth weight infants (VLBWIs) was determined using the Neonatal Research Network of Japan database. RESULTS: The response rates in 2005, 2010, and 2015 were 86.8% (230/265), 64.5% (185/287), and 82.8% (236/285) of units, respectively. The use of patient-triggered ventilation for initial management significantly increased from 50% of units in 2005 to 91% in 2015. By contrast, decreased use of high-frequency oscillatory ventilation (HFOV) from 72% to 65% and that of nasal continuous positive airway pressure from 79% to 68% were reported. The proportion of units where the upper limit of targeted blood oxygen saturation before a diagnosis of BPD was set to ≥95% decreased substantially from 92% to 56% over the 10-year period. Despite these changes in management of BPD, the incidence of BPD among VLBWIs in Japan was increasing over a decade. CONCLUSION: This survey demonstrated that there were various changes in practice regarding the prevention or treatment of BPD in Japan. Continuous surveys are required to understand the current clinical situation, and research is needed to develop and evaluate a novel treatment for BPD in premature infants.


Assuntos
Displasia Broncopulmonar/terapia , Displasia Broncopulmonar/epidemiologia , Displasia Broncopulmonar/prevenção & controle , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Recém-Nascido de muito Baixo Peso , Japão/epidemiologia , Masculino , Oxigênio/sangue , Inquéritos e Questionários
20.
Arch Dis Child Fetal Neonatal Ed ; 105(4): 399-404, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31685527

RESUMO

OBJECTIVE: Compare rates of hypoxaemia during transpyloric and gastric feedings in very preterm infants with severe bronchopulmonary dysplasia. DESIGN: N-of-1 multiple crossover trials with individual patient and pooled data analyses. SETTING: Level IV intensive care nursery. PATIENTS: Infants receiving positive airway pressure between 36 and 55 weeks postmenstrual age were enrolled between December 2014-July 2016. INTERVENTION: N-of-1 trial consisting of two blocks, each with a 4-day gastric and 4-day transpyloric feeding period assigned in random order. MAIN OUTCOME MEASURES: The primary outcome was the frequency of daily intermittent hypoxaemic events (SpO2 ≤80% lasting 10-180 s). Secondary outcomes included the daily proportion of time with an SpO2 ≤80% and mean daily fraction of inspired oxygen. RESULTS: Of 15 infants, 13 completed the trial and 2 stopped early for transient worsening in respiratory status during gastric feedings. In the intention-to-treat analyses, transpyloric feedings resulted in increased rates of intermittent hypoxaemia in five infants, greater time per day in hypoxaemia in three infants and more supplemental oxygen use in three infants. One infant received more supplemental oxygen during gastric feedings. The remaining study outcomes were similar between the feeding routes in all other infants. Pooling all data, transpyloric feedings resulted in a higher frequency of intermittent hypoxaemic events (median 7.5/day (IQR 1-23.5) vs 3/day (1-11); adjusted incidence rate ratio 1.8, 95% CI 1.3 to 2.5) and a greater proportion of daily hypoxaemia time (median 0.8% (IQR 0.1-2.3) vs 0.4% (0.07-1.8); adjusted mean difference 1.6, 95% CI 1.1 to 2.5). CONCLUSIONS: Transpyloric compared with gastric feedings modestly increased rates of hypoxaemia among study participants. TRIAL REGISTRATION NUMBER: NCT02142621.


Assuntos
Displasia Broncopulmonar/terapia , Nutrição Enteral/métodos , Hipóxia/epidemiologia , Doenças do Prematuro/terapia , Medicina de Precisão/métodos , Estudos Cross-Over , Feminino , Humanos , Incidência , Recém-Nascido , Recém-Nascido Prematuro , Masculino
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