Predischarge death or lung transplantation in tracheostomy and ventilator dependent grade 3 bronchopulmonary dysplasia.

BACKGROUND: Premature infants surviving beyond a postmenstrual age (PMA) of 36 weeks with severe or grade 3 bronchopulmonary dysplasia (sBPD) have significant predischarge mortality. The in-hospital mortality for BPD supported by invasive mechanical ventilation beyond 36 weeks PMA is not well described. The role of lung transplantation in treating severe BPD is uncertain. We studied our experience over 20 years to better define the predischarge mortality of infants with progressive grade 3 BPD and whether lung transplant is a feasible intervention. METHODS: Data were obtained from a retrospective review of medical records from Children's Minnesota over a 20-year period (1997-2016). Inclusion criteria included prematurity <32 weeks PMA, BPD, tracheostomy for chronic respiratory failure, and survival beyond 36 weeks PMA. Collected data included perinatal demographics, in-hospital medications and interventions, level of respiratory support, and outcomes. RESULTS: In all, 2374 infants were identified who survived beyond 36 weeks PMA with a diagnosis of <32 weeks gestation prematurity and BPD. Of these, 143/2374 (6.0%) survived beyond 36 weeks PMA and required invasive mechanical ventilation with subsequent tracheostomy for management. Among these patients, discharge to home with tracheostomy occurred in 127/143 (88.8%), and predischarge death or lung transplantation occurred in 16/143 (11.2%). Deteriorating cardiopulmonary status was associated with pulmonary hypertension, prolonged hypoxemic episodes and the need for deep sedation or neuromuscular relaxation. Three of four patients referred for lung transplantation had >5-year survival, chronic allograft rejection, and mild to moderate developmental delays. CONCLUSIONS: Chronic respiratory failure requiring invasive mechanical ventilation for grade 3 BPD is associated with significant morbidity and mortality. For selected patients and their families, timely referral for lung transplantation is a viable option for end-stage grade 3 BPD. As in other infants receiving solid organ transplants, long-term issues with co-morbidities and special needs persist into childhood.

Respiratory culture growth and 3-years lung health outcomes in children with bronchopulmonary dysplasia and tracheostomies.

BACKGROUND: While bacteria identification on respiratory cultures is associated with poor short-term outcomes in children with bronchopulmonary dysplasia (BPD) and tracheostomies, the influence on longer-term respiratory support needs remains unknown. OBJECTIVE: To determine if respiratory culture growth of pathogenic organisms is associated with ongoing need for respiratory support, decannulation, and death at 3 years posttracheostomy placement in children with BPD and tracheostomies. METHODS: This single center, retrospective cohort study included infants and children with BPD and tracheostomies placed 2010-2018 and ≥1 respiratory culture obtained in 36 months posttracheostomy. Primary predictor was any pathogen identified on respiratory culture. Additional predictors were any Pseudomonas aeruginosa and chronic P. aeruginosa identification. Outcomes included continued use of respiratory support (e.g., oxygen, positive pressure), decannulation, and death at 3 years posttracheostomy. We used Poisson regression models to examine the relationship between respiratory organisms and outcomes, controlling for patient-level covariates and within-patient clustering. RESULTS: Among 170 children, 59.4% had a pathogen identified, 28.8% ever had P. aeruginosa, and 3.5% had chronic P. aeruginosa. At 3 years, 33.1% of alive children required ongoing respiratory support and 24.8% achieved decannulation; 18.9% were deceased. In adjusted analysis, any pathogen and P. aeruginosa were not associated with ongoing respiratory support or mortality. However, P. aeruginosa was associated with decreased decannulation probability (adjusted risk ratio 0.48, 95% CI 0.23-0.98). Chronic P. aeruginosa was associated with lower survival probability. CONCLUSION: Our findings suggest that respiratory pathogens including P. aeruginosa may not promote long-term respiratory dysfunction, but identification of P. aeruginosa may delay decannulation.

Lung Transplantation for Bronchopulmonary Dysplasia.

BACKGROUND: Patients with bronchopulmonary dysplasia (BPD) have poor respiratory trajectories and are at increased risk of lung function decline with age. Lung transplant (LTx) is a possible treatment option for this growing patient population, but little has been published on LTx in this patient group. RESEARCH QUESTION: What are the characteristics of patients with BPD who are listed for LTx? How do waitlist and post-LTx outcomes for BPD compare with LTx for other diagnoses? STUDY DESIGN AND METHODS: The United Network for Organ Sharing (UNOS) registry was queried for patients of all ages listed for or who underwent LTx (2000-2020). Descriptive analysis, waitlist outcomes, and post-LTx survival at 1, 5, and 10 years were assessed comparing patients with BPD vs LTx patients with other diagnoses. Post-LTx survival for patients with BPD born in the pre-surfactant era (pre-SE, before 1990) and those born in the post-surfactant era (post-SE) was compared. Propensity score matching was performed to control for the risk factors and match patients with BPD with other LTx patients on a 1:1 ratio. RESULTS: BPD was reported in 65 patients, of whom 32 (49.2%) underwent LTx. Patients with BPD at listing were younger than those with other diagnoses (median age, 21 [interquartile range, 5-31] years vs 57 [45-63] years; P < .001), and more were likely to receive mechanical ventilation at listing (23% vs 3.7%; P < .001). Patients with BPD had an FEV1 of 17% compared with 34% predicted in other patients (P = .002). Patients with BPD had an overall similar post-LTx survival compared with patients with other diagnoses (P = .106), even following propensity score matching (P = .41). INTERPRETATION: LTx for BPD has increased over the last 20 years. Patients with BPD have similar post-LTx outcomes compared with those of other patient populations in the modern era. Thus, LTx could be considered for patients with BPD experiencing progressive respiratory deterioration.

Factors That Impact the Timing and Removal of Gastrostomy Placement/Nissen Fundoplication in Children with Bronchopulmonary Dysplasia.

OBJECTIVE: The study aimed to identify factors that impact timing of gastrostomy placement/removal and Nissen fundoplication (NF) in infants with bronchopulmonary dysplasia (BPD). STUDY DESIGN: Clinical data were reviewed retrospectively from patients recruited from the Johns Hopkins Bronchopulmonary Dysplasia Clinic (January 1, 2014-December 31, 2018). RESULTS: Patients with gastrostomy tubes (GTs) placed in the neonatal intensive care unit (NICU) were older at discharge (p < 0.001) and less likely to have abnormal upper gastrointestinal series findings (p = 0.005) than those with GTs placed after NICU discharge. Patients with NF had lower mean gestational ages (p = 0.011), longer NICU stays (p = 0.019), more frequent home ventilation requirements (p = 0.005), and greater likelihood of pulmonary hypertension (p = 0.032) compared with those without. Median age of GT removal was 61.6 months. Patients with GTs were weaned from supplemental oxygen and/or home ventilation before GT removal (p < 0.001). CONCLUSION: Patients with GT/NF were more medically complex than those with GT alone. Patients were more likely to be weaned from home respiratory support before GT removal. KEY POINTS: · Patients with GT/NF were more medically complex than those with GT alone.. · Patients were more likely to be weaned from home respiratory support before GT removal.. · Patients with GTs placed in NICU were older at discharge and less likely to have abnormal upper gastrointestinal series result..

Traqueostomía en prematuros con displasia broncopulmonar grave / Tracheostomy in premature infants with severe bronchopulmonary dysplasia

Los recién nacidos con displasia broncopulmonar dependientes de ventilación mecánica a las 36 semanas, corresponden en general a prematuros menores de 27 semanas con morbilidad grave: enterocolitis, infecciones, retinopatía, retraso en el crecimiento y secuelas del neurodesarrollo. Si la extubación no es posible entre las 40 y 50 semanas, se indica una traqueostomía, normalmente acompañada de una gastrostomía. La decisión depende del apoyo ventilatorio, de la morbilidad asociada (neurológica, hipertensión pulmonar, lesiones de la vía aérea) y del grado de desnutrición. La traqueostomía optimiza el manejo ventilatorio, disminuye la necesidad de sedación, facilita la movilidad, la neurorrehabilitación y el alta al hogar en ventilación domiciliaria. La edad óptima de ejecución no está estandarizada, pero hay evidencia que muestra beneficios en el neurodesarrollo si se realiza antes de los 120 días de vida. La mayoría de los prematuros traqueostomizados son manejados en domicilio y a los 5 años ya se encuentran decanulados.

Newborns with bronchopulmonary dysplasia (BPD) dependent on mechanical ventilation at 36 weeks, generally correspond to newborns younger than 27 weeks with severe morbidity: enterocolitis, infections, retinopathy, growth retardation and neurodevelopmental sequelae. If extubation is not possible at 40-50 weeks post menstrual age, a tracheostomy is indicated, usually accompanied by a gastrostomy. The decision depends on ventilatory support, associated morbidity (neurological, pulmonary hypertension, airway lesions) and the degree of malnutrition. Tracheostomy optimizes ventilatory management, reduces the need for sedation, facilitates mobility, neurorehabilitation, and discharge on home ventilation. The optimal age for tracheostomy is not standardized, but there is evidence showing neurodevelopmental benefits if it is performed before 120 days. Most tracheostomized newborns are managed at home and at 5 years of age they are already decannulated.

Posterior tracheopexy for preterm infants with severe bronchopulmonary dysplasia and severe tracheobronchomalacia: A case series.

We report a series of four patients with severe bronchopulmonary dysplasia (BPD) who underwent posterior tracheopexy for severe tracheomalacia (TM). While posterior tracheopexy is an established surgical treatment for TM associated with tracheoesophageal fistula, it has not been previously described in TM associated with BPD. There were no significant intraoperative or postoperative complications from the surgeries. Three of the four patients required tracheostomy and mechanical ventilation, which may reflect the degree of lung disease and other multisystem comorbidities in these patients. More investigation is needed to determine whether posterior tracheopexy is an effective surgical option for TM related to BPD.

Racial Influences on Pediatric Tracheostomy Outcomes.

OBJECTIVES/HYPOTHESIS: To determine the impact of race on outcomes after pediatric tracheostomy. STUDY DESIGN: Retrospective case series. METHODS: A case series of tracheostomies at an urban, tertiary care children's hospital between 2014 and 2019 was conducted. Children were grouped by race to compare neurocognition, mortality, and decannulation rate. RESULTS: A total of 445 children with a median age at tracheostomy of 0.46 (interquartile range [IQR]: 0.97) years were studied. The cohort was 32% Hispanic, 31% White, 30% Black, 2.9% Asian, and 4.3% other race. Black compared to White children had a lower median birth weight (2,022 vs. 2,449 g, P = .005), were more often extremely premature (≤28 weeks gestation: 62% vs. 57%, P = .007), and more frequently had bronchopulmonary dysplasia (BPD) (35% vs. 17%, P = .002). Hispanic compared to Black children had higher median birth weight (2,529 g, P < .001), less extreme prematurity (44%, P < .001), and less BPD (21%, P = .04). The proportion of Black children was higher (30% vs. 19%, P < .001), while the proportion of Hispanic children with a tracheostomy was lower (32% vs. 42%, P = .003) compared to the racial distribution of all pediatric admissions. Racial differences were not seen for rates of severe neurocognitive disability (P = .51), decannulation (P = .17), or death (P = .92) after controlling for age, sex, prematurity, and ventilator dependence. CONCLUSION: Black children disproportionately underwent tracheostomy and had a higher comorbidity burden than White or Hispanic children. Hispanic children had proportionally fewer tracheostomies. Neurocognitive ability, decannulation, and mortality were similar for all races implying that health disparities by race may not change long-term outcomes after pediatric tracheostomy. Laryngoscope, 132:1118-1124, 2022.

Qualitative indications for tracheostomy and chronic mechanical ventilation in patients with severe bronchopulmonary dysplasia.

BACKGROUND: The decision to pursue chronic mechanical ventilation involves a complex mix of clinical and social considerations. Understanding the medical indications to pursue tracheostomy would reduce the ambiguity for both providers and families and facilitate focus on appropriate clinical goals. OBJECTIVE: To describe potential indications to pursue tracheostomy and chronic mechanical ventilation in infants with severe BPD (sBPD). STUDY DESIGN: We surveyed centers participating in the Children's Hospitals Neonatal Consortium to describe their approach to proceed with tracheostomy in infants with sBPD. We requested a single representative response per institution. Question types were fixed form and free text responses. RESULTS: The response rate was high (31/34, 91%). Tracheostomy was strongly considered when: airway malacia was present, PCO2 ≥ 76-85 mmHg, FiO2 ≥ 0.60, PEEP ≥ 9-11 cm H2O, respiratory rate ≥ 61-70 breaths/min, PMA ≥ 44 weeks, and weight <10th %ile at 44 weeks PMA. CONCLUSIONS: Understanding the range of indications utilized by high level NICUs around the country to pursue a tracheostomy in an infant with sBPD is one step toward standardizing consensus indications for tracheostomy in the future.

Application Prospects of Mesenchymal Stem Cell Therapy for Bronchopulmonary Dysplasia and the Challenges Encountered.

Bronchopulmonary dysplasia (BPD) is a common chronic lung disease in premature babies, especially affecting those with very low or extremely low birth weights. Survivors experience adverse lung and neurological defects including cognitive dysfunction. This impacts the prognosis of children with BPD and may result in developmental delays. The currently available options for the treatment of BPD are limited owing to low efficacy or several side effects; therefore, there is a lack of effective treatments for BPD. The treatment for BPD must help in the repair of damaged lung tissue and promote further growth of the lung tissue. In recent years, the emergence of stem cell therapy, especially mesenchymal stem cell (MSC) therapy, has improved the treatment of BPD to a great extent. This article briefly reviews the advantages, research progress, and challenges faced with the use of MSCs in the treatment of BPD. Stem cell therapy is beneficial as it repairs damaged tissues by reducing inflammation, fibrosis, and by acting against oxidative stress damage. Experimental trials have also proven that MSCs provide a promising avenue for BPD treatment. However, there are challenges such as the possibility of MSCs contributing to tumorous growths, the presence of heterogeneous cell populations resulting in variable efficacy, and the ethical considerations regarding the use of this treatment in humans. Therefore, more research must be conducted to determine whether MSC therapy can be approved as a treatment option for BPD.

Tracheostomy trends in preterm infants with bronchopulmonary dysplasia in the United States: 2008-2017.

OBJECTIVE: To determine the trends in tracheostomy placement and resource use in preterm infants less than or equal to 30 weeks gestational age (GA) with bronchopulmonary dysplasia (BPD) in the United States from 2008 to 2017. STUDY DESIGN: This was a retrospective, serial cross-sectional study using data from the NIS. Inclusion criteria were: GA less than or equal to 30 weeks, hospitalization at less than or equal to 28 days of age, assignment of International Classification of Diseases, Ninth Revision, Clinical Modification (ICD9-CM) or ICD10-CM codes for BPD and tracheostomy. Trends in tracheostomy and resource utilization were assessed using Jonckheere-Terpstra test. p-value < .05 was considered significant. RESULTS: Overall, 987 out of 68,953 (1.4%) hospitalizations with BPD had tracheostomy. Characteristics of the study population: 60.8% were male, 68.4% less than or equal to 26 weeks GA, 43.8% White, 60.5% with Medicaid or self-pay, 65.2% in the Midwest and South census regions of the United States, and 45.7% had gastrostomy tube placement. Tracheostomy placement (expressed as per 100,000 live births) decreased from 2.7 in 2008 to 1.9 in 2011. Thereafter, it increased from 1.9 in 2011 to 3.5 in 2017 (p < .001). GA less than or equal to 24 weeks was significantly associated with increased odds of tracheostomy placement. Median length of stay increased significantly from 170 to 231 days while median inflation adjusted hospital cost increased significantly from $323,091 in 2008-2009 to $687,141 between 2008-2009 and 2016-2017. CONCLUSION: Although tracheostomy placement among preterm hospitalizations with BPD was rare, the frequency of its placement and its associated resource utilization significantly increased during the study period. Future studies should probe the reasons and factors behind these trends.

A Longitudinal Analysis of Outcomes in Tracheostomy Placement Among Preterm Infants.

OBJECTIVES: To study a case series of preterm and extremely preterm infants, comparing their decannulation and survival rates after tracheostomy. METHODS: We performed a single-institution longitudinal study of preterm infants with a tracheostomy. Infants were categorized as premature (born > 28 weeks and < 37 weeks) and extremely premature (born ≤ 28 weeks). Decannulation and survival rates were determined using the Kaplan-Meier method. Neurocognitive quality of life (QOL) was reported as normal, mild/moderately, and severely impaired. Statistical significance was set at P < .05. RESULTS: This study included 240 patients. Of those, 111 were premature and 129 were extremely preterm. The median age (interquartile range) at tracheostomy was 4.8 months (0.4). Premature infants were more likely than extremely preterm to have airway obstruction (54% vs. 32%, P < .001); whereas extremely preterm infants were more likely to have bronchopulmonary dysplasia (68% vs. 15%, P < .001) and to be ventilation-dependent (68% vs. 54%, P < .001). The 5-year decannulation rate for premature infants was 46% and for extremely preterm was 64%. The 5-year survival rate post-tracheostomy for preterm was 79% and for extremely preterm was 73%. The log-rank test of equality showed that decannulation and survival were similar (P > .05) for both groups, even after controlling for potentially confounding factors like race, age, gender, birth weight, and age at tracheostomy. For neurocognitive QOL, 47% of patients survived with severely impaired QOL after tracheostomy. Preterm had 56% with severely impaired QOL and extremely preterm had 40% with severely impaired QOL (P = .03). CONCLUSION: This study demonstrated that the time to decannulation and the likelihood of survival did not vary among premature and extremely premature infants even when controlling for other confounding variables. LEVEL OF EVIDENCE: 3b Laryngoscope, 131:417-422, 2021.

Lung transplant in a recipient with tracheal bronchus.

We describe the intraoperative surgical management of tracheal bronchus encountered in a lung transplant recipient.

Lung Transplantation for Bronchopulmonary Dysplasia in Adults: A Clinical and Pathologic Study of 3 Cases.

Bronchopulmonary dysplasia (BPD) is usually seen in premature infants who require mechanical ventilation and oxygen therapy for acute respiratory distress. Although most patients wean from oxygen therapy by the ages of 2 to 3, rehospitalization for respiratory problems is common in these patients in adulthood. There have been few studies that document the long-term outcomes of BPD survivors and information about the pulmonary function and radiographic findings of adult BPD are limited. Data on pathologic features of adult BPD are scarce. Three adult patients who underwent recent lung transplantation for BPD from 2 institutions were identified. Clinical data including clinical presentation, chest radiographic images, pulmonary function tests, cardiac catheterization, and echocardiography were retrieved from the electronic medical records. Hematoxylin and eosin and selective elastic stained sections of the explant lungs were examined. CD31 immunohistochemical stain is performed on representative sections. All 3 cases had similar clinical and radiologic features including the history of prematurity and long-term mechanical ventilation after birth, hyperexpanded lungs with air trapping and mosaic attenuation on chest computed tomographic scan, severe obstructive changes on pulmonary function test, and pulmonary hypertension. Pathologic examination showed common features including enlarged and simplified alveoli, peribronchial, subpleural, and interlobular septal fibrosis, narrowing/obliteration of the small airways by elastosis and muscular hypertrophy, thickening of venous walls by fibromuscular hyperplasia, and bronchitis/bronchiolitis. Cholesterol granulomas were seen in 2 cases. The common pathologic findings in the lungs explain the clinical and radiologic findings. Future studies are warranted to further characterize the clinical and pathologic features of adult BPD to develop optimal management strategies for these patients.

Tracheostomy in Extremely Preterm Neonates in the United States: A Cross-Sectional Analysis.

OBJECTIVES/HYPOTHESIS: Bronchopulmonary dysplasia (BPD) and invasive respiratory support is increasing among extremely preterm neonates. Yet, it is unclear if there is a corresponding increase in tracheostomies. We hypothesize that in extremely preterm neonates with BPD, the incidence of tracheostomy has increased. STUDY DESIGN: Retrospective cross-sectional analysis. METHODS: We analyzed the 2006 to 2012 Kids' Inpatient Databases (KID) for hospital discharges of nonextremely preterm neonates (gestational age >28 weeks and <37 weeks or birth weight >1,500 g) and extremely preterm neonates (gestational age ≤28 weeks or birth weight ≤1,500 g). We studied tracheostomy placement trends in these two populations to see if they are increasing among extremely preterm neonates, especially those with BPD. RESULTS: The study included 1,418,681 preterm neonates (52% male, 50% white, 19% black, 20% Hispanic, 4.2% Asian), of whom 118,676 (8.4%) were extremely preterm. A total of 2,029 tracheostomies were performed, of which 803 (0.68%) were in extremely preterm neonates. The estimated percent change of occurrence of extremely preterm neonates with BPD increased 17% between 2006 and 2012, and tracheostomy placement increased 31%. Amongst all who received tracheostomies, mortality rate was higher in extremely preterm neonates compared to nonextremely preterm neonates (18% vs. 14%, P = .05). However, in extremely preterm neonates, those with tracheostomies had a lower mortality rate compared to those without (18% vs. 24%, P = .002). CONCLUSIONS: Extremely preterm neonates, compared to nonextremely preterm neonates, experienced a marked increase in tracheostomies placed from 2006 to 2012 as well as an increased incidence of BPD, confirming our primary study hypothesis. LEVEL OF EVIDENCE: 4 Laryngoscope, 130: 2056-2062, 2020.

Impact of tracheostomy on language and cognitive development in infants with severe bronchopulmonary dysplasia.

OBJECTIVE: The impact of tracheostomy on language and cognitive development in infants with severe bronchopulmonary dysplasia (BPD) is not known. We hypothesize that tracheostomy has an independent negative impact on language and cognitive development in infants with severe BPD. STUDY DESIGN: This is a retrospective cohort study of de-identified data of infants with severe BPD who received tracheostomy at <2 years of age, compared with infants with severe BPD without tracheostomy. The primary outcomes measured were total language and cognitive scores at 2-3 years of age as determined by Bayley Scales of Infant and Toddler Development, 3rd Edition. RESULTS: A total of 26 patients with tracheostomies and 28 patients without tracheostomies were analyzed. There was no significant difference in total language development or cognitive development between patients with tracheostomies and those without. Insurance status had an effect on language and cognition while controlling for trach status. CONCLUSIONS: Tracheostomy does not independently impact the language and cognitive development of infants with severe BPD.

So You Want to Give Stem Cells to Babies? Neonatologists and Parents' Views to Optimize Clinical Trials.

OBJECTIVE: To identify barriers and enablers that may influence parents' and neonatologists' participation in clinical trials of mesenchymal stromal cells for bronchopulmonary dysplasia. STUDY DESIGN: This qualitative study involved one-on-one semistructured interviews with parents of extremely preterm infants (n = 18) and neonatologists (n = 16). Interview guides and directed content analysis were framed using the theoretical domains framework, a tool specifically developed for implementation research to identify influences on behavior. RESULTS: Key barriers for parents included their lack of knowledge about clinical trial processes in general, stem cells, and concerns about their risks and side effects. Importantly, parents preferred to be approached for recruitment directly by a neonatologist, either before delivery or 1 or 2 weeks after birth. However, the majority of neonatologists felt that approaching parents was not part of their role. Neonatologists reported competing priorities, time commitment, costs, and lack of institutional support as significant barriers to their ability to recruit patients. CONCLUSIONS: By integrating stakeholders early into the development of a clinical trial of mesenchymal stromal cell therapy, we identified and can address important barriers to enrollment. Some identified barriers were unanticipated and could have compromised recruitment had they not been identified by this study. We suggest that this approach can be used more broadly for other early phase clinical trials in pediatrics.

A nationwide survey on tracheostomy for very-low-birth-weight infants in Japan.

OBJECTIVES: Tracheostomy is indicated for very-low-birth-weight infants (VLBWIs) with prolonged respiratory problems during the perinatal period. The objective of this study is to clarify the epidemiology and risk factors in VLBWIs with tracheostomy after birth in Japan. METHODS: A total of 40 806 VLBWIs were registered in the Neonatal Research Network of Japan database from 2003 to 2012. Among them, 34 674 infants (85%) survived over 28 days after birth and were subjected to this study. The clinical variables at birth, outcomes at hospital discharge and associated factors for tracheostomy were examined. RESULTS: The proportion of VLBWIs with tracheostomy did not increase during the study period (mean 36 cases per year, 0.93%). The rate of in-hospital death over 28 days after birth did not differ between tracheostomized and non-tracheostomized infants (2/324, 0.6% vs 314/34 350, 0.9%). Tracheostomized infants more frequently had severe or moderate bronchopulmonary dysplasia (BPD) (75.5% vs 26.0%, P < 0.01) and longer hospitalization (229 days vs 83 days, P < 0.01) than non-tracheostomized infants. Tracheostomized patients showed higher comorbidities with hypoxic ischemic encephalopathy (odds ratio [OR] 10.98, P < 0.01), muscular disease (OR 10.95, P < 0.01), severe or moderate BPD (OR 7.79, P < 0.01), chromosomal abnormality (OR 4.43, P < 0.01) or sepsis (OR 1.78, P < 0.05) at hospital discharge than non-tracheostomized patients. CONCLUSION: We demonstrated the non-increasing rate in tracheostomy for VLBWIs and such cases were associated with an excellent survival in Japan. These data provide evidence that more attentive care must be practiced in order to reduce the pulmonary and neuromuscular burdens of VLBWIs at birth.

Improved growth and developmental activity post tracheostomy in preterm infants with severe BPD.

OBJECTIVES: To examine growth, sedation needs, and participation in developmental activities before and after tracheostomy among infants with severe bronchopulmonary dysplasia. METHODS: Retrospective analysis of infants born at <32 weeks' gestation or birth weights <1500 g with severe BPD who underwent tracheostomy placement between January 1, 2010 and December 31, 2016 in a quaternary referral newborn and infant intensive care unit. Changes in growth parameters and frequency/type of participation in physical therapy sessions performed during the 4-weeks before tracheostomy and 4-weeks after the first tracheostomy tube change were compared. RESULTS: A total of 72 patient were included in the study. Average weekly gain in weight, length, and head circumference were significantly higher during the 4-week period after compared to before tracheostomy. The most significant change occurred for linear growth (0.71 ± 0.40 cm/wk pre vs 0.97 ± 0.48 cm/wk pre, P < 0.001). Median Z score improved for weight (pre -1.42 [-3,10, -0.33] vs post -0.91 [-2.7, 0.27], P < 0.001), length (pre -3.07 [-4.39, -1.31] vs post -1.95 [-3.83, -0.93], P < 0.001) and weight-to-length ratio (pre 1.66 [0.58, 2.55] vs post 1.32 [0.17, 2.2], P = 0.02). Participation in developmental therapies significantly improved post tracheostomy (pre vs post: 5.2 ± 2.9 vs 8.7 ± 4.3 sessions performed over 4 weeks, P < 0.0001). Physical therapy sessions more often promoted developmental skill acquisition after tracheostomy compared to facilitating physiologic stability before tracheostomy. Daily sedation requirements decreased post tracheostomy. CONCLUSIONS: Tracheostomy was associated with improved proportional growth and increased participation in activities promoting developmental skill acquisition and reduced daily sedation requirements in preterm infants with severe BPD.

Acute Post-Tracheostomy Clinical Decompensations in Infants-Are There Predictive Markers?

OBJECTIVE: To report on the population of infants receiving a tracheostomy, identify acute post-tracheostomy clinical decompensations, and seek predictive markers associated with acute complications following the placement of a tracheostomy. STUDY DESIGN: Retrospective deidentified clinical data was provided by the Infant Pulmonary Data Repository at Children's Mercy Hospital, Kansas City. Data from infants undergoing tracheostomy from January 1, 2008 through September 30, 2016 were divided into one of two study groups based on clinical correlations: (1) no acute decompensations within 72 hours post-tracheostomy or (2) acute clinical decompensation defined as sustained escalation of respiratory care within the 72 hours following tracheostomy. RESULTS: Thirty-four percent of infants undergoing tracheostomy during this period developed acute post-tracheostomy clinical decompensations. Elevated pre-tracheostomy positive end expiratory pressure, mean airway pressure, and echocardiogram findings suggestive of pulmonary hypertension (PH) or ventricular dysfunction were associated with acute post-tracheostomy clinical decompensations. Additionally acute post-tracheostomy clinical decompensation was associated with higher rate of death prior to discharge. CONCLUSION: Infants requiring higher respiratory support and infants with PH or ventricular dysfunction are at risk of acute post-tracheostomy clinical decompensation, thus identifying these patients may lead to better pre-tracheostomy counseling and potentially targeted treatments to decrease this risk.

Stromal derived factor-1 mediates the lung regenerative effects of mesenchymal stem cells in a rodent model of bronchopulmonary dysplasia.

BACKGROUND: Mesenchymal stem cells (MSCs) attenuate lung injury in experimental models of bronchopulmonary dysplasia (BPD). Stromal derived factor-1 (SDF-1), a chemokine secreted by MSCs, modulates angiogenesis and stem cell recruitment. Here we tested the hypothesis that SDF-1 mediates MSC protective effects in experimental BPD by modulating angiogenesis. METHODS: SDF-1 was knocked down in MSCs using lentiviral vectors carrying anti-SDF-1 short hairpin RNA (MSC-SDF KD). Non-silencing short hairpin RNA was used as control (MSC-NS control). Newborn rats exposed to normoxia or hyperoxia (FiO2 = 0.85) for 3 weeks, were randomly assigned to receive a single intra-tracheal injection (IT) of MSC-NS control or MSC-SDF KD (1 × 106 cells/50 µl) or placebo on postnatal day 7. The degree of alveolarization, lung angiogenesis, inflammation, and pulmonary hypertension (PH) were assessed at postnatal day 21. RESULTS: Administration of IT MSC-NS control improved lung alveolarization, angiogenesis and inflammation, and attenuated PH in newborn rats with hyperoxia-induced lung injury (HILI). In contrast, knockdown of SDF-1 in MSCs significantly reduced their beneficial effects on alveolarization, angiogenesis, inflammation and PH. CONCLUSIONS: The therapeutic benefits of MSCs in neonatal HILI are in part mediated by SDF-1, through anti-inflammatory and angiogenesis promoting mechanisms. Therapies directly targeting this chemokine may provide a novel strategy for the treatment of BPD.