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  1. Article: Mechanical ventilation: invasive versus noninvasive.

    Brochard, L

    The European respiratory journal. Supplement

    2003  Volume 47, Page(s) 31s–37s

    Abstract: ... noninvasive" ventilation (NIV) techniques, using patient/ventilator interfaces in the form of facial masks, have been ... factor in success seems to be the early delivery of noninvasive ventilation during the course ... of respiratory failure. Noninvasive ventilation allows many of the complications associated ...

    Abstract Mechanical ventilation is the most widely used supportive technique in intensive care units. Several forms of external support for respiration have long been described to assist the failing ventilatory pump, and access to lower airways through tracheostomy or endotracheal tubes had constituted a major advance in the management of patients with respiratory distress. More recently, however, new "noninvasive" ventilation (NIV) techniques, using patient/ventilator interfaces in the form of facial masks, have been designed. The reasons for promoting NIV include a better understanding of the role of ventilatory pump failure in the indications for mechanical ventilation, the development of ventilatory modalities able to work in synchrony with the patient, and the extensive recognition of complications associated with endotracheal intubation and standard mechanical ventilation. NIV has been used primarily for patients with acute hypercapnic ventilatory failure, and especially for acute exacerbation of chronic obstructive pulmonary disease. In this population, the use of NIV is associated with a marked reduction in the need for endotracheal intubation, a decrease in complication rate, a reduced duration of hospital stay and a substantial reduction in hospital mortality. Similar benefits have also been demonstrated in patients with asphyxic forms of acute cardiogenic pulmonary oedema. In patients with primarily hypoxemic forms of respiratory failure, the level of success of NIV is more variable, but major benefits have also been demonstrated in selected populations with no contraindications such as multiple organ failure, loss of consciousness or haemodynamic instability. One important factor in success seems to be the early delivery of noninvasive ventilation during the course of respiratory failure. Noninvasive ventilation allows many of the complications associated with mechanical ventilation to be avoided, especially the occurrence of nosocomial infections. The current use of noninvasive ventilation is growing up, and is becoming a major therapeutic tool in the intensive care unit.
    MeSH term(s) Acute Disease ; Female ; Humans ; Intubation, Intratracheal/adverse effects ; Intubation, Intratracheal/methods ; Laryngeal Masks ; Male ; Oxygen Inhalation Therapy/methods ; Prognosis ; Pulmonary Edema/diagnosis ; Pulmonary Edema/mortality ; Pulmonary Edema/therapy ; Pulmonary Gas Exchange ; Respiration, Artificial/adverse effects ; Respiration, Artificial/methods ; Respiratory Function Tests ; Respiratory Insufficiency/diagnosis ; Respiratory Insufficiency/mortality ; Respiratory Insufficiency/therapy ; Risk Assessment ; Sensitivity and Specificity ; Severity of Illness Index ; Survival Analysis
    Language English
    Publishing date 2003-11-04
    Publishing country England
    Document type Comparative Study ; Journal Article ; Review
    ZDB-ID 1020376-x
    ISSN 0904-1850
    ISSN 0904-1850
    DOI 10.1183/09031936.03.00050403
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Noninvasive versus conventional mechanical ventilation in bronchiolitis.

    Wang, Daniel H / Adamko, Darryl / Shaw, Adam / Holt, Tanya / Hansen, Gregory

    Minerva pediatrics

    2023  Volume 75, Issue 2, Page(s) 305–307

    MeSH term(s) Humans ; Respiration, Artificial ; Bronchiolitis/therapy ; Noninvasive Ventilation
    Language English
    Publishing date 2023-04-18
    Publishing country Italy
    Document type Journal Article
    ZDB-ID 3062664-X
    ISSN 2724-5780
    ISSN (online) 2724-5780
    DOI 10.23736/S2724-5276.21.06319-9
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Invasive versus non-invasive paediatric home mechanical ventilation: review of the international evolution over the past 24 years.

    Toussaint, Michel / van Hove, Olivier / Leduc, Dimitri / Ansay, Lise / Deconinck, Nicolas / Fauroux, Brigitte / Khirani, Sonia

    Thorax

    2024  Volume 79, Issue 6, Page(s) 581–588

    Abstract: Background: Home mechanical ventilation (HMV) is the treatment for chronic hypercapnic alveolar ... hypoventilation. The proportion and evolution of paediatric invasive (IMV) and non-invasive (NIV) HMV across ... and Cardio-Resp disorders. Children with NMD still receiving primary invasive HMV were mainly type ...

    Abstract Background: Home mechanical ventilation (HMV) is the treatment for chronic hypercapnic alveolar hypoventilation. The proportion and evolution of paediatric invasive (IMV) and non-invasive (NIV) HMV across the world is unknown, as well as the disorders and age of children using HMV.
    Methods: Search of Medline/PubMed for publications of paediatric surveys on HMV from 2000 to 2023.
    Results: Data from 32 international reports, representing 8815 children (59% boys) using HMV, were analysed. A substantial number of children had neuromuscular disorders (NMD; 37%), followed by cardiorespiratory (Cardio-Resp; 16%), central nervous system (CNS; 16%), upper airway (UA; 13%), other disorders (Others; 10%), central hypoventilation (4%), thoracic (3%) and genetic/congenital disorders (Gen/Cong; 1%). Mean age±SD (range) at HMV initiation was 6.7±3.7 (0.5-14.7) years. Age distribution was bimodal, with two peaks around 1-2 and 14-15 years. The number and proportion of children using NIV was significantly greater than that of children using IMV (n=6362 vs 2453, p=0.03; 72% vs 28%, p=0.048), with wide variations among countries, studies and disorders. NIV was used preferentially in the preponderance of children affected by UA, Gen/Cong, Thoracic, NMD and Cardio-Resp disorders. Children with NMD still receiving primary invasive HMV were mainly type I spinal muscular atrophy (SMA). Mean age±SD at initiation of IMV and NIV was 3.3±3.3 and 8.2±4.4 years (p<0.01), respectively. The rate of children receiving additional daytime HMV was higher with IMV as compared with NIV (69% vs 10%, p<0.001). The evolution of paediatric HMV over the last two decades consists of a growing number of children using HMV, in parallel to an increasing use of NIV in recent years (2020-2023). There is no clear trend in the profile of children over time (age at HMV). However, an increasing number of patients requiring HMV were observed in the Gen/Cong, CNS and Others groups. Finally, the estimated prevalence of paediatric HMV was calculated at 7.4/100 000 children.
    Conclusions: Patients with NMD represent the largest group of children using HMV. NIV is increasingly favoured in recent years, but IMV is still a prevalent intervention in young children, particularly in countries indicating less experience with NIV.
    MeSH term(s) Humans ; Child ; Respiration, Artificial/methods ; Respiration, Artificial/statistics & numerical data ; Noninvasive Ventilation ; Home Care Services ; Adolescent ; Infant ; Child, Preschool
    Language English
    Publishing date 2024-05-20
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 204353-1
    ISSN 1468-3296 ; 0040-6376
    ISSN (online) 1468-3296
    ISSN 0040-6376
    DOI 10.1136/thorax-2023-220888
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Comparison of high flow oxygen therapy versus noninvasive mechanical ventilation for successful weaning from invasive ventilation in children: An observational study.

    Celik, Nur Berna / Tanyildiz, Murat / Yetimakman, Filiz / Kesici, Selman / Bayrakci, Benan

    Medicine

    2022  Volume 101, Issue 39, Page(s) e30889

    Abstract: ... the efficacy of high-flow nasal cannula (HFNC) and noninvasive mechanical ventilation (NIMV) on extubation ... Logistic Organ Dysfunction scores, oxygenation index, mechanical ventilation length of stay (LOS), HFNC ... ventilator-associated pneumonia, and longer length of stay in the ICU and hospital. In this study, we aimed to evaluate ...

    Abstract Post-extubation respiratory failure is associated with a poor prognosis due to increased ventilator-associated pneumonia, and longer length of stay in the ICU and hospital. In this study, we aimed to evaluate the efficacy of high-flow nasal cannula (HFNC) and noninvasive mechanical ventilation (NIMV) on extubation success in children. A total of 48 patients, aged between 1 month and 18 years, who were weaned to either NIMV or HFNC were included. Patients who had tracheostomy or were not weaned and underwent unplanned extubation were excluded. Age, gender, anthropometric parameters, Pediatric Risk of Mortality and Pediatric Logistic Organ Dysfunction scores, oxygenation index, mechanical ventilation length of stay (LOS), HFNC/NIMV LOS, Modified Downes-Silverman score (MDS), and venous blood gas parameters, pediatric intensive care unit (PICU) LOS were recorded. 24 patients were extubated to NIMV, and 24 patients to HFNC. HFNC LOS and NIMV LOS were similar (P = .621). The failure rates at the 48th hour of HFNC and NIMV were 33% (n = 8), and 33% respectively (n = 8) (P = 1.0). PICU LOS and mortality rate was also similar (P = .06, P = .312 respectively). MDS decreased significantly in both groups (P < .001, P = .02 respectively). Changes in blood gas parameters and MDS within the first 48-hour of device application were similar between the 2 groups. HFNC is not inferior to NIMV in patients with extubation difficulty or those expected to have such difficulty in terms of treatment success, PICU LOS, and mortality. Therefore, HFNC appears to be a weaning technique alternative to NIMV after extubation.
    MeSH term(s) Airway Extubation ; Cannula ; Child ; Humans ; Infant ; Noninvasive Ventilation ; Oxygen ; Oxygen Inhalation Therapy/methods ; Respiration, Artificial ; Respiratory Insufficiency/therapy
    Chemical Substances Oxygen (S88TT14065)
    Language English
    Publishing date 2022-09-30
    Publishing country United States
    Document type Journal Article ; Observational Study
    ZDB-ID 80184-7
    ISSN 1536-5964 ; 0025-7974
    ISSN (online) 1536-5964
    ISSN 0025-7974
    DOI 10.1097/MD.0000000000030889
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Non-invasive ventilation versus mechanical ventilation in hypoxemic patients with COVID-19.

    Forrest, Iain S / Jaladanki, Suraj K / Paranjpe, Ishan / Glicksberg, Benjamin S / Nadkarni, Girish N / Do, Ron

    Infection

    2021  Volume 49, Issue 5, Page(s) 989–997

    Abstract: ... have led to the use of non-invasive ventilation (NIV) in hypoxemic patients, which has not been studied ... Purpose: Limited mechanical ventilators (MV) during the Coronavirus disease (COVID-19) pandemic ... well. We aimed to assess the association of NIV versus MV with mortality and morbidity during ...

    Abstract Purpose: Limited mechanical ventilators (MV) during the Coronavirus disease (COVID-19) pandemic have led to the use of non-invasive ventilation (NIV) in hypoxemic patients, which has not been studied well. We aimed to assess the association of NIV versus MV with mortality and morbidity during respiratory intervention among hypoxemic patients admitted with COVID-19.
    Methods: We performed a retrospective multi-center cohort study across 5 hospitals during March-April 2020. Outcomes included mortality, severe COVID-19-related symptoms, time to discharge, and final oxygen saturation (SpO2) at the conclusion of the respiratory intervention. Multivariable regression of outcomes was conducted in all hypoxemic participants, 4 subgroups, and propensity-matched analysis.
    Results: Of 2381 participants with laboratory-confirmed SARS-CoV-2, 688 were included in the study who were hypoxemic upon initiation of respiratory intervention. During the study period, 299 participants died (43%), 163 were admitted to the ICU (24%), and 121 experienced severe COVID-19-related symptoms (18%). Participants on MV had increased mortality than those on NIV (128/154 [83%] versus 171/534 [32%], OR = 30, 95% CI 16-60) with a mean survival of 6 versus 15 days, respectively. The MV group experienced more severe COVID-19-related symptoms [55/154 (36%) versus 66/534 (12%), OR = 4.3, 95% CI 2.7-6.8], longer time to discharge (mean 17 versus 7.1 days), and lower final SpO2 (92 versus 94%). Across all subgroups and propensity-matched analysis, MV was associated with a greater OR of death than NIV.
    Conclusions: NIV was associated with lower respiratory intervention mortality and morbidity than MV. However, findings may be liable to unmeasured confounding and further study from randomized controlled trials is needed to definitively determine the role of NIV in hypoxemic patients with COVID-19.
    MeSH term(s) COVID-19 ; Cohort Studies ; Humans ; Noninvasive Ventilation ; Respiration, Artificial ; Retrospective Studies ; SARS-CoV-2
    Language English
    Publishing date 2021-06-05
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 185104-4
    ISSN 1439-0973 ; 0300-8126 ; 0173-2129
    ISSN (online) 1439-0973
    ISSN 0300-8126 ; 0173-2129
    DOI 10.1007/s15010-021-01633-6
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Survival and Healthcare Costs with Invasive Mechanical Ventilation versus Noninvasive Ventilation in Patients with Dementia Admitted with Pneumonia and Respiratory Failure.

    Teno, Joan M / Sullivan, Donald R / Bunker, Jen / Gozalo, Pedro

    Annals of the American Thoracic Society

    2022  Volume 19, Issue 8, Page(s) 1364–1370

    Abstract: Rationale: ...

    Abstract Rationale:
    MeSH term(s) Activities of Daily Living ; Chronic Disease ; Dementia/complications ; Dementia/therapy ; Health Care Costs ; Hospital Mortality ; Hospitalization ; Humans ; Noninvasive Ventilation/adverse effects ; Pneumonia/complications ; Pneumonia/therapy ; Respiration, Artificial ; Respiratory Insufficiency/etiology ; Retrospective Studies ; Sepsis ; United States
    Language English
    Publishing date 2022-02-07
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2717461-X
    ISSN 2325-6621 ; 1943-5665 ; 2325-6621
    ISSN (online) 2325-6621 ; 1943-5665
    ISSN 2325-6621
    DOI 10.1513/AnnalsATS.202110-1161OC
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article: Spontaneous breathing trial with pressure support on positive end-expiratory pressure and extensive use of non-invasive ventilation versus T-piece in difficult-to-wean patients from mechanical ventilation: a randomized controlled trial.

    Mezidi, Mehdi / Yonis, Hodane / Chauvelot, Louis / Deniel, Guillaume / Dhelft, François / Gaillet, Maxime / Noirot, Ines / Folliet, Laure / Chabert, Paul / David, Guillaume / Danjou, William / Baboi, Loredana / Bettinger, Clotilde / Bernon, Pauline / Girard, Mehdi / Provoost, Judith / Bazzani, Alwin / Bitker, Laurent / Richard, Jean-Christophe

    Annals of intensive care

    2024  Volume 14, Issue 1, Page(s) 59

    Abstract: ... of post-extubation non-invasive ventilation (NIV) (extensively-assisted weaning) would shorten the time ... from mechanical ventilation.: Methods: The study is a single-center prospective open label, randomized controlled ... intubated patients mechanically ventilated for more than 24 h who failed their first SBT using TP ...

    Abstract Background: The aim of this study is to assess whether a strategy combining spontaneous breathing trial (SBT) with both pressure support (PS) and positive end-expiratory pressure (PEEP) and extended use of post-extubation non-invasive ventilation (NIV) (extensively-assisted weaning) would shorten the time until successful extubation as compared with SBT with T-piece (TP) and post-extubation NIV performed in selected patients as advocated by guidelines (standard weaning), in difficult-to-wean patients from mechanical ventilation.
    Methods: The study is a single-center prospective open label, randomized controlled superiority trial with two parallel groups and balanced randomization with a 1:1 ratio. Eligible patients were intubated patients mechanically ventilated for more than 24 h who failed their first SBT using TP. In the extensively-assisted weaning group, SBT was performed with PS (7 cmH
    Results: From May 2019 to March 2023, 98 patients were included and randomized in the study (49 in each group). Four patients were excluded from the intention-to-treat population (2 in both groups); therefore, 47 patients were analyzed in each group. The extensively-assisted weaning group had a higher median age (68 [58-73] vs. 62 [55-71] yrs.) and similar sex ratio (62% male vs. 57%). Time until successful extubation was not significantly different between extensively-assisted and standard weaning groups (median, 172 [50-436] vs. 95 [47-232] hours, Cox hazard ratio for successful extubation, 0.88 [95% confidence interval: 0.55-1.42] using the standard weaning group as a reference; p = 0.60). All secondary outcomes were not significantly different between groups.
    Conclusion: An extensively-assisted weaning strategy did not lead to a shorter time to successful extubation than a standard weaning strategy. Trial registration The trial was registered on ClinicalTrials.gov (NCT03861117), on March 1, 2019, before the inclusion of the first patient. https://clinicaltrials.gov/study/NCT03861117 .
    Language English
    Publishing date 2024-04-17
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 2617094-2
    ISSN 2110-5820
    ISSN 2110-5820
    DOI 10.1186/s13613-024-01290-6
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  8. Article ; Online: Mechanical Power Delivered by Noninvasive Ventilation Contributes to Physio-Anatomical and Clinical Responses to Early Versus Late Proning in COVID-19 Pneumonia.

    Musso, Giovanni / Taliano, Claudio / Paschetta, Elena / De Iuliis, Marco / Fonti, Caterina / Vianou, Ines Sarah / Druetta, Marta / Riedo, Federica / Ferraris, Andrea / Tirabassi, Gloria

    Critical care medicine

    2023  Volume 51, Issue 9, Page(s) 1185–1200

    Abstract: Objectives: To study: 1) the effect of prone position (PP) on noninvasive ventilation (NIV ... delivered mechanical power (MP) and 2) the impact of MP on physio-anatomical and clinical responses to early ... versus late PP in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia.: Design ...

    Abstract Objectives: To study: 1) the effect of prone position (PP) on noninvasive ventilation (NIV)-delivered mechanical power (MP) and 2) the impact of MP on physio-anatomical and clinical responses to early versus late PP in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia.
    Design: Nonrandomized trial with inverse probability of treatment weighted-matched groups.
    Setting: HUMANITAS Gradenigo Sub-ICU.
    Patients: One hundred thirty-eight SARS-CoV-2 pneumonia patients with moderate-to-severe acute hypoxemic respiratory failure (Pa o2 /F io2 ratio < 200 mm Hg) receiving NIV from September 1, 2020, to February 28, 2021 (Ethics approval: ISRCTN23016116).
    Interventions: Early PP or late PP or supine position.
    Measurements and main results: Respiratory parameters were hourly recorded. Time-weighted average MP values were calculated for each ventilatory session. Gas exchange parameters and ventilatory ratio (VR) were measured 1 hour after each postural change. Lung ultrasonographic scores and circulating biomarkers were assessed daily. MP delivered during the initial 24 hours of NIV (MP [first 24 hr]) was the primary exposure variable. Primary outcomes: 28-day endotracheal intubation and death. Secondary outcomes: oxygen-response, C o2 -response, ultrasonographic, and systemic inflammatory biomarker responses after 24 hours of NIV. Fifty-eight patients received early PP + NIV, 26 late PP + NIV, and 54 supine NIV. Early PP group had lower 28-day intubation and death than late PP (hazard ratio [HR], 0.35; 95% CI, 0.19-0.69 and HR, 0.26; 95% CI, 0.07-0.67, respectively) and supine group. In Cox multivariate analysis, (MP [first 24 hr]) predicted 28-day intubation (HR, 1.70; 95% CI, 1.25-2.09; p = 0.009) and death (HR, 1.51; 95% CI, 1.19-1.91; p = 0.007). Compared with supine position, PP was associated with a 35% MP reduction. VR, ultrasonographic scores, and inflammatory biomarkers improved after 24 hours of NIV in the early PP, but not in late PP or supine group. A MP (first 24 hr) greater than or equal to 17.9 J/min was associated with 28-day death (area under the curve, 0.92; 95% CI, 0.88-0.96; p < 0.001); cumulative hours of MP greater than or equal to 17.9 J/min delivered before PP initiation attenuated VR, ultrasonographic, and biomarker responses to PP.
    Conclusions: MP delivered by NIV during initial 24 hours predicts clinical outcomes. PP curtails MP, but cumulative hours of NIV with MP greater than or equal to 17.9 J/min delivered before PP initiation attenuate the benefits of PP.
    MeSH term(s) Humans ; COVID-19/therapy ; Lung ; Noninvasive Ventilation ; Respiration, Artificial ; Respiratory Insufficiency/therapy ; SARS-CoV-2
    Language English
    Publishing date 2023-05-26
    Publishing country United States
    Document type Clinical Trial ; Journal Article
    ZDB-ID 197890-1
    ISSN 1530-0293 ; 0090-3493
    ISSN (online) 1530-0293
    ISSN 0090-3493
    DOI 10.1097/CCM.0000000000005915
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article: Outcomes in Patients with Acute Hypoxemic Respiratory Failure Secondary to COVID-19 Treated with Noninvasive Respiratory Support versus Invasive Mechanical Ventilation.

    Fisher, Julia M / Subbian, Vignesh / Essay, Patrick / Pungitore, Sarah / Bedrick, Edward J / Mosier, Jarrod M

    medRxiv : the preprint server for health sciences

    2022  

    Abstract: ... in-hospital mortality (37% for invasive mechanical ventilation and 39% for noninvasive respiratory support). Initial ... mechanical ventilation first and 53% received initial noninvasive respiratory support. There was an overall 38 ... mechanical ventilation (HR: 1.61, p < 0.0001, 95% CI: 1.33 - 1.94). However, patients on initial noninvasive respiratory ...

    Abstract Purpose: The goal of this study was to compare noninvasive respiratory support to invasive mechanical ventilation as the initial respiratory support in COVID-19 patients with acute hypoxemic respiratory failure.
    Methods: All patients admitted to a large healthcare network with acute hypoxemic respiratory failure associated with COVID-19 and requiring respiratory support were eligible for inclusion. We compared patients treated initially with noninvasive respiratory support (noninvasive positive pressure ventilation by facemask or high flow nasal oxygen) with patients treated initially with invasive mechanical ventilation. The primary outcome was time-to-in-hospital death analyzed using an inverse probability of treatment weighted Cox model adjusted for potential confounders. Secondary outcomes included unweighted and weighted assessments of mortality, lengths-of-stay (intensive care unit and hospital) and time-to-intubation.
    Results: Over the study period, 2354 patients met inclusion criteria. Nearly half (47%) received invasive mechanical ventilation first and 53% received initial noninvasive respiratory support. There was an overall 38% in-hospital mortality (37% for invasive mechanical ventilation and 39% for noninvasive respiratory support). Initial noninvasive respiratory support was associated with an increased hazard of death compared to initial invasive mechanical ventilation (HR: 1.61, p < 0.0001, 95% CI: 1.33 - 1.94). However, patients on initial noninvasive respiratory support also experienced an increased hazard of leaving the hospital sooner, but the hazard ratio waned with time (HR: 0.97, p < 0.0001, 95% CI: 0.96 - 0.98).
    Conclusion: These data show that the COVID-19 patients with acute hypoxemic respiratory failure initially treated with noninvasive respiratory support had an increased hazard of in-hospital death.
    Language English
    Publishing date 2022-12-20
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2022.12.19.22283704
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  10. Article ; Online: Hippocampal epigenetic and insulin-like growth factor alterations in noninvasive versus invasive mechanical ventilation in preterm lambs.

    Ke, Xingrao / Xing, Bohan / Dahl, Mar Janna / Alvord, Jeremy / McKnight, Robert A / Lane, Robert H / Albertine, Kurt H

    Pediatric research

    2021  Volume 90, Issue 5, Page(s) 998–1008

    Abstract: ... damage during invasive mechanical ventilation (IMV). Damage is manifest, in part, by learning and memory ... insulin-like growth factor 1 (IGF1). A gentler ventilation strategy is noninvasive respiratory support (NRS). We tested ... to better neurodevelopmental outcomes later in life versus IMV. Also, duration of IMV is directly related ...

    Abstract Background: The brain of chronically ventilated preterm human infants is vulnerable to collateral damage during invasive mechanical ventilation (IMV). Damage is manifest, in part, by learning and memory impairments, which are hippocampal functions. A molecular regulator of hippocampal development is insulin-like growth factor 1 (IGF1). A gentler ventilation strategy is noninvasive respiratory support (NRS). We tested the hypotheses that NRS leads to greater levels of IGF1 messenger RNA (mRNA) variants and distinct epigenetic profile along the IGF1 gene locus in the hippocampus compared to IMV.
    Methods: Preterm lambs were managed by NRS or IMV for 3 or 21 days. Isolated hippocampi were analyzed for IGF1 mRNA levels and splice variants for promoter 1 (P1), P2, and IGF1A and 1B, DNA methylation in P1 region, and histone covalent modifications along the gene locus.
    Results: NRS had significantly greater levels of IGF1 P1 (predominant transcript), and 1A and 1B mRNA variants compared to IMV at 3 or 21 days. NRS also led to more DNA methylation and greater occupancy of activating mark H3K4 trimethylation (H3K4me
    Conclusions: NRS leads to distinct IGF1 mRNA variant levels and epigenetic profile in the hippocampus compared to IMV.
    Impact: Our study shows that 3 or 21 days of NRS of preterm lambs leads to distinct IGF1 mRNA variant levels and epigenetic profile in the hippocampus compared to IMV. Preterm infant studies suggest that NRS leads to better neurodevelopmental outcomes later in life versus IMV. Also, duration of IMV is directly related to hippocampal damage; however, molecular players remain unknown. NRS, as a gentler mode of respiratory management of preterm neonates, may reduce damage to the immature hippocampus through an epigenetic mechanism.
    MeSH term(s) Animals ; Animals, Newborn ; DNA Methylation ; Epigenesis, Genetic ; Female ; Hippocampus/metabolism ; Histones/metabolism ; Male ; Promoter Regions, Genetic ; Respiration, Artificial/methods ; Sheep ; Somatomedins/genetics ; Somatomedins/metabolism
    Chemical Substances Histones ; Somatomedins
    Language English
    Publishing date 2021-02-18
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 4411-8
    ISSN 1530-0447 ; 0031-3998
    ISSN (online) 1530-0447
    ISSN 0031-3998
    DOI 10.1038/s41390-020-01305-5
    Database MEDical Literature Analysis and Retrieval System OnLINE

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