Dataset Information

Mechanical ventilation injury and repair in extremely and very preterm lungs.

ABSTRACT:

Background

Extremely preterm infants often receive mechanical ventilation (MV), which can contribute to bronchopulmonary dysplasia (BPD). However, the effects of MV alone on the extremely preterm lung and the lung's capacity for repair are poorly understood.

Aim

To characterise lung injury induced by MV alone, and mechanisms of injury and repair, in extremely preterm lungs and to compare them with very preterm lungs.

Methods

Extremely preterm lambs (0.75 of term) were transiently exposed by hysterotomy and underwent 2 h of injurious MV. Lungs were collected 24 h and at 15 d after MV. Immunohistochemistry and morphometry were used to characterise injury and repair processes. qRT-PCR was performed on extremely and very preterm (0.85 of term) lungs 24 h after MV to assess molecular injury and repair responses.

Results

24 h after MV at 0.75 of term, lung parenchyma and bronchioles were severely injured; tissue space and myofibroblast density were increased, collagen and elastin fibres were deformed and secondary crest density was reduced. Bronchioles contained debris and their epithelium was injured and thickened. 24 h after MV at 0.75 and 0.85 of term, mRNA expression of potential mediators of lung repair were significantly increased. By 15 days after MV, most lung injury had resolved without treatment.

Conclusions

Extremely immature lungs, particularly bronchioles, are severely injured by 2 h of MV. In the absence of continued ventilation these injured lungs are capable of repair. At 24 h after MV, genes associated with injurious MV are unaltered, while potential repair genes are activated in both extremely and very preterm lungs.

SUBMITTER: Brew N

PROVIDER: S-EPMC3660361 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Publications

Mechanical ventilation injury and repair in extremely and very preterm lungs.

Brew Nadine N Hooper Stuart B SB Zahra Valerie V Wallace Megan M Harding Richard R

PloS one 20130521 5

<h4>Background</h4>Extremely preterm infants often receive mechanical ventilation (MV), which can contribute to bronchopulmonary dysplasia (BPD). However, the effects of MV alone on the extremely preterm lung and the lung's capacity for repair are poorly understood.<h4>Aim</h4>To characterise lung injury induced by MV alone, and mechanisms of injury and repair, in extremely preterm lungs and to compare them with very preterm lungs.<h4>Methods</h4>Extremely preterm lambs (0.75 of term) were trans ...[more]

PMID: 23704953

Similar Datasets

Project description:BackgroundBronchopulmonary dysplasia (BPD) is closely associated with ventilator-induced lung injury (VILI) in very preterm infants. The greatest risk of VILI may be in the immediate period after birth, when the lungs are surfactant deficient, still partially filled with liquid and not uniformly aerated. However, there have been very few studies that have examined this immediate post-birth period and identified the initial injury-related pathways that are activated. We aimed to determine if the early response genes; connective tissue growth factor (CTGF), cysteine rich-61 (CYR61) and early growth response 1 (EGR1), were rapidly induced by VILI in preterm lambs and whether ventilation with different tidal volumes caused different inflammatory cytokine and early response gene expression.MethodsTo identify early markers of VILI, preterm lambs (132 d gestational age; GA, term approximately 147 d) were resuscitated with an injurious ventilation strategy (V(T) 20 mL/kg for 15 min) then gently ventilated (5 mL/kg) for 15, 30, 60 or 120 min (n = 4 in each). To determine if early response genes and inflammatory cytokines were differentially regulated by different ventilation strategies, separate groups of preterm lambs (125 d GA; n = 5 in each) were ventilated from birth with a V(T) of 5 (VG5) or 10 mL/kg (VG10) for 135 minutes. Lung gene expression levels were compared to levels prior to ventilation in age-matched control fetuses.ResultsCTGF, CYR61 and EGR1 lung mRNA levels were increased approximately 25, 50 and 120-fold respectively (p < 0.05), within 30 minutes of injurious ventilation. VG5 and VG10 caused significant increases in CTGF, CYR61, EGR1, IL1- , IL-6 and IL-8 mRNA levels compared to control levels. CTGF, CYR61, IL-6 and IL-8 expression levels were higher in VG10 than VG5 lambs; although only the IL-6 and CYR61 mRNA levels reached significance.ConclusionCTGF, CYR61 and EGR1 may be novel early markers of lung injury and mechanical ventilation from birth using relatively low tidal volumes may be less injurious than using higher tidal volumes.

Project description:BACKGROUND:The relation between mechanical ventilation (MV) and bronchopulmonary dysplasia (BPD) - a common disease in extremely premature newborn (PTNB) - is well stabilished, but is unknown, however, how much time under MV influences the severity of the disease. AIM:To define the duration under MV with greater chance to develop moderate to severe BPD in extremely PTNB and to compare clinical outcomes before and during hospitalization among patients with mild and moderate to severe BPD. METHODS:Fifty-three PTNB were separated into mild and moderate to severe BPD groups and their data were analyzed. Time under MV with a greater chance of developing moderate to severe BPD was estimated by the ROC curve. Perinatal and hospitalization outcomes were compared between groups. A logistic regression was performed to verify the influence of variables associated to moderate to severe BPD development, such as pulmonary hypertension (PH), gender, gestational age (GA) and weight at birth, as well the time under MV found with ROC curve. The result of ROC curve was validated using an independent sample (n =?16) by Chi-square test. RESULTS:Time under MV related to a greater chance of developing moderate to severe BPD was 36?days. Moderate to severe BPD group had more males (14 vs 5, p =?0,047), longer time under MV (43 vs 19?days, p <?0,001), more individuals with PH (12 vs 3, p =?0,016), worse retinopathy of prematurity (grade 3, 2 vs 11, p =?0,003), longer hospital length of stay (109 vs 81,5?days, p <?0,001), greater PMA (41 vs 38?weeks, p <?0,001) and weight (2620 vs 2031?g, p <?0,001) at discharge and the mild BPD group had more CPAP use prior to MV (12 vs 7, p =?0,043). Among all variables included in logistic regression, only PH and MV?<?36?days were significant in the model, explaining 72% of variation in moderate to severe BPD development. In the validation sample, prevalence of preterm infants who needed MV for more than 36?days in the moderate to severe BPD group was 100% (n =?6) and 0% in mild BPD group (p =?0,0001). CONCLUSION:Time under MV related to moderate to severe BPD development is 36?days, and worst outcomes are related to disease severity. PH and time under MV for more than 36?days are related to development of moderate to severe BPD.

Dataset Information

Mechanical ventilation injury and repair in extremely and very preterm lungs.

Background

Aim

Methods

Results

Conclusions

Publications

Mechanical ventilation injury and repair in extremely and very preterm lungs.

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