Chronic Pulmonary Insufficiency of Prematurity: Developing Optimal Endpoints for Drug Development

Steinhorn, Robin H.; Davis, Jonathan M.; Göpel, Wolfgang; Jobe, Alan H.; Abman, Steven H.; Laughon, Matthew M.; Bancalari, Eduardo; Aschner, Judy L.; Ballard, Roberta A.; Greenough, Anne; Storari, Linda; Thomson, M.; Ariagno, Ronald L.; Fabbri, L.; Turner, Mark A.

doi:10.1016/j.jpeds.2017.08.006

Cited by 117 publications

(101 citation statements)

References 50 publications

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“…Moreover, BPD may not be the best outcome for the intrinsic limitations of its definition. 33 However, finding the best way to define chronic respiratory morbidity was beyond our scopes. Conversely, we wanted to capture a description of the respiratory status at term and couple it with clinical follow-up.…”

Section: Discussionmentioning

confidence: 99%

“…BPD definition provides a functional description that is not correlated with specific mechanisms. BPD and susceptibility to VAP are likely to be different in patients of different age or comorbidities, but we cannot provide reliable subgroup analysis given our population size. Moreover, BPD may not be the best outcome for the intrinsic limitations of its definition .…”

Section: Discussionmentioning

confidence: 99%

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Short‐ and long‐term respiratory outcomes in neonates with ventilator‐associated pneumonia

Dell’Orto

Raschetti

Centorrino

et al. 2019

Pediatric Pulmonology

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Background and Objective Ventilator‐associated pneumonia (VAP) is a common nosocomial infection in critical care settings and might have important long‐term consequences in neonates. Our aim is to clarify the short‐ and long‐term respiratory outcomes of neonates affected by VAP. Methods Prospective, population‐based, cohort study with 12 months follow‐up based on clinical examinations and diary‐based respiratory morbidity score, conducted in an academic tertiary referral neonatal unit with dedicated follow‐up program. Results A total of 199 inborn neonates consecutively ventilated for at least 48 hours were eligible for the study. One hundred fifty‐one were finally enrolled and classified as “exposed” or “unexposed” to VAP, if they fulfilled (or not) VAP criteria once during their stay. Bronchopulmonary dysplasia (BPD) incidence was significantly higher in exposed (75%) than in unexposed babies (26.8%; relative risk [RR]: 2.8 [1.9‐4.0]; AdjRR: 3.5 [1.002‐12.7]; P = .049; number needed to harm = 2.07), although the composite BPD/mortality did not differ. Exposed patients showed longer intensive care unit stay (87 [43‐116] vs 14 [8‐52] days; St.β = 0.24; P < .0001) and duration of ventilation (15 [10‐25] vs 5 [4‐8] days; St.β = 0.29; P < .0001) than unexposed neonates. Exposed patients also showed less ventilator‐free days (11 [5‐17.7] vs 22 [14‐24] days; St.β = −0.15; P = .05) compared to unexposed. Respiratory infections, use of drugs, rehospitalization for respiratory reasons, home oxygen therapy, their composite outcome, and diary‐based clinical respiratory morbidity score were similar between the cohorts. Conclusion Neonatal VAP seems associated to higher incidence of BPD, longer ventilation, and intensive care stay but it does not affect long‐term respiratory morbidity.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Short‐ and long‐term respiratory outcomes in neonates with ventilator‐associated pneumonia

Dell’Orto

Raschetti

Centorrino

et al. 2019

Pediatric Pulmonology

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“…Moreover, there are no LUS data describing 'developing BPD' or the new concept of chronic pulmonary insufficiency of prematurity, that may provide new interesting areas of application for LUS. 60 Malformations LUS has been used to describe congenital pulmonary airway malformations (CPAM), which have a variable appearance (a large or micro-cystic lesion or irregular consolidations) in line with the four histological types described in the most recent CPAM classification. 61,62 The gold standard to diagnose lung malformations remains the CT-scan, though LUS may allow to suspect CPAM in the absence of an antenatal diagnosis.…”

Section: Broncho-pulmonary Dysplasiamentioning

confidence: 99%

Point-of-care lung ultrasound in neonatology: classification into descriptive and functional applications

et al. 2018

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Lung ultrasound (LUS) is the latest amongst imaging techniques: it is a radiation-free, inexpensive, point-of-care tool that the clinician can use at the bedside. This review summarises the rapidly growing scientific evidence on LUS in neonatology, dividing it into descriptive and functional applications. We report the description of the main ultrasound features of neonatal respiratory disorders and functional applications of LUS aiming to help a clinical decision (such as surfactant administration, chest drainage etc). Amongst the functional applications, we propose SAFE (Sonographic Algorithm for liFe threatening Emergencies) as a standardised protocol for emergency functional LUS in critical neonates. SAFE has been funded by a specific grant issued by the European Society for Paediatric Research. Future potential development of LUS in neonatology might be linked to its quantitative evaluation: we also discuss available data and research directions using computer-aided diagnostic techniques. Finally, tools and opportunities to teach LUS and expand the research network are briefly presented.

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“…The clinical definition was adapted over time, mainly based on oxygen dependency at 36 weeks corrected age 23. At present, it is clear that a revision is needed, because of suboptimal prediction of long-term outcome and the necessity to identify infants with severe lung disease failing prior to 36 weeks corrected age 24. Current therapies are unable to stem the multiple insults leading to BPD.…”

Section: Surfactant Antenatal Steroids and Bpd—attack Of The Clonesmentioning

confidence: 99%

Stem cell-based therapies in neonatology: a new hope

Thébaud

2018

Arch Dis Child Fetal Neonatal Ed

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Despite progress made in neonatal intensive care, complications of extreme preterm birth still contribute as the main cause of death to children below 5 years of age. Stem cell-based therapies-mesenchymal stromal cells in particular-offer a new hope in preventing and/or restoring organ damage in extreme preterm infants. Early phase clinical trials, fueled by promising preclinical studies on lung and brain injury, have begun. While the enthusiasm in the neonatal community is palpable, much more needs to be learnt about cell-based therapies. Maintaining the balance between temptation and a cautious, evidence-based approach will be critical for cell therapies to fulfil their promise in substantially improving the outcome of extreme preterm infants.

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Chronic Pulmonary Insufficiency of Prematurity: Developing Optimal Endpoints for Drug Development

Cited by 117 publications

References 50 publications

Short‐ and long‐term respiratory outcomes in neonates with ventilator‐associated pneumonia

Short‐ and long‐term respiratory outcomes in neonates with ventilator‐associated pneumonia

Point-of-care lung ultrasound in neonatology: classification into descriptive and functional applications

Stem cell-based therapies in neonatology: a new hope

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