Postnatal lung development and its impairment by glucocorticoids

Tschanz, Stefan A.; Burri, Peter H.

doi:10.1002/ppul.19502308128

Cited by 33 publications

(19 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In animal models, DEX has been shown to impair septation and alveolarization (17)(18)(19)(20). Mitchell et al (45) reported impaired gas transfer at rest and during exercise as measured by D L,CO in prematurely-born children with BPD but not in those without BPD.…”

Section: Discussionmentioning

confidence: 99%

“…Neonatal DEX exposure has been associated with impaired somatic growth early in life (17)(18)(19)(20), and concomitant lung growth may also be impaired. A study by Yeh et al (46) suggested that long-term growth impairment was associated with postnatal DEX exposure at 6 years of age.…”

Section: Discussionmentioning

confidence: 99%

“…The beneficial effects of postnatal corticosteroids on the lung are believed to be related to reduced inflammation (14-16). However, experiments in animals suggest that corticosteroid exposure during critical periods of lung development may impair alveolarization (17)(18)(19)(20). Furthermore, follow-up studies of VLBW children suggest adverse effects of postnatal DEX exposure, specifically impaired growth and neurologic development (21)(22).…”

Section: Introductionmentioning

confidence: 99%

“…Mitchell et al (45) reported impaired gas transfer at rest and during exercise as measured by D L,CO in prematurely-born children with BPD but not in those without BPD. Consequently, the negative effects that DEX may have on alveolarization may be countered by its positive effects of reducing exposure to mechanical ventilation and supplemental oxygen, and the subsequent risk for BPD.Neonatal DEX exposure has been associated with impaired somatic growth early in life (17)(18)(19)(20), and concomitant lung growth may also be impaired. A study by Yeh et al(46) suggested that long-term growth impairment was associated with postnatal DEX exposure at 6 years of age.…”

mentioning

confidence: 99%

See 3 more Smart Citations

Follow-up Study of a Randomized Controlled Trial of Postnatal Dexamethasone Therapy in Very Low Birth Weight Infants: Effects on Pulmonary Outcomes at Age 8 to 11 Years

Nixon

Washburn

Schechter

et al. 2007

The Journal of Pediatrics

View full text Add to dashboard Cite

Objective-To determine if postnatal dexamethasone (DEX) exposure affects pulmonary outcomes at school-age in children born with very low birth weight (VLBW).Study design-Follow-up study of 68 VLBW children who participated in a randomized controlled trial (RCT) of postnatal DEX. Pulmonary function was assessed by spirometry. Current asthma status was obtained from a parent.Results-Sixty-eight % of the placebo group had below normal forced expiratory volume in 1 second (FEV 1 ) compared to 40% of the DEX group (X 2 = 4.84, p=.03), with trends for lower forced vital capacity (FVC) and FEV 1 values in the placebo group. Fifty % of placebo group and 34% of DEX group had below normal FEV 1 /FVC (X 2 =1.59; p =.21). Parent-reported prevalence of asthma did not differ between groups. Logistic regression analysis suggested that the positive effects of DEX on pulmonary function at follow-up were mediated in part by shortened postnatal exposure to mechanical ventilation.Conclusions-Postnatal DEX exposure was associated with higher expiratory flow with no adverse effects on pulmonary outcomes at school-age. The prevalence of asthma and impaired pulmonary function underscore the influence of neonatal illness on health at school age, and stress the importance of repeated follow-up examinations of these children. Keywordsprematurity; chronic lung disease; bronchopulmonary dysplasia; children; corticosteroid; lung function asthma Approximately 1.5% of infants are born prematurely each year with very low birth weight (VLBW) (birth weight < 1501 grams) (1), and about 19-23% of these infants will develop chronic lung disease (CLD) (2,3). A diagnosis of CLD has been associated with greater Address correspondence to: Patricia A. Nixon, Ph.D., Wake Forest University, HES Dept. P.O. Box 7868, Winston-Salem, NC 27109-7868, Phone (336) Fax (336) 758-4680, Email nixonpa@wfu.edu. edited by AJ and WFB Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. hospital readmission rates for respiratory morbidity during the first five years of life (4), increased odds of asthma (4) and respiratory symptoms in childhood (5), and reduced pulmonary function in infancy (6), childhood (7,8), adolescence (9), and young adulthood (10) compared to their VLBW peers without CLD. Systematic reviews indicate that treatment of VLBW infants with corticosteroids, primarily dexamethasone (DEX), in the first few weeks of life significantly decreases duration of ventilator dependence and the incidence of CLD (11-13). The beneficial effects of postnatal corticosteroids on the lung are believed to be related to reduce...

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Follow-up Study of a Randomized Controlled Trial of Postnatal Dexamethasone Therapy in Very Low Birth Weight Infants: Effects on Pulmonary Outcomes at Age 8 to 11 Years

Nixon

Washburn

Schechter

et al. 2007

The Journal of Pediatrics

View full text Add to dashboard Cite

show abstract

“…The early postnatal use of glucocorticoids is often motivated by a positive effect on lung maturation in preterm born babies, who otherwise stand a high risk of developing chronic lung disease also called bronchopulmonary dysplasia. However, as a side effect, it has been demonstrated in a number of animal models that glucocorticoids may impair postnatal lung maturation and growth (1)(2)(3)(4)(5).…”

mentioning

confidence: 99%

Impairment of Rat Postnatal Lung Alveolar Development by Glucocorticoids: Involvement of the p21CIP1 and p27KIP1 Cyclin-Dependent Kinase Inhibitors

et al. 2002

View full text Add to dashboard Cite

It has been shown that glucocorticoids accelerate lung development by limiting alveolar formation resulting from a premature maturation of the alveolar septa. Based on these data, the aim of the present work was to analyze the influence of dexamethasone on cell cycle control mechanisms during postnatal lung development. Cell proliferation is regulated by a network of signaling pathways that converge to the key regulator of cell cycle machinery: the cyclin-dependent kinase (CDK) system. The activity of the various cyclin/CDK complexes can be modulated by the levels of the cyclins and their CDKs, and by expression of specific CDK inhibitors (CKIs). In the present study, newborn rats were given a 4-d treatment with dexamethasone (0.1-0.01 g/g body weight dexamethasone sodium phosphate daily on d 1-4), or saline. Morphologically, the treatment caused a significant thinning of the septa and an acceleration of lung maturation on d 4. Study of cyclin/CDK system at d 1-36 documented a transient down-regulation of cyclin/CDK complex activities at d 4 in the dexamethasone-treated animals. Analysis of the mechanisms involved suggested a role for the CKIs p21 CIP1 and p27 KIP1 . Indeed, we observed an increase in p21 CIP1and p27 KIP1 protein levels on d 4 in the dexamethasone-treated animals. By contrast, no variations in either cyclin and CDK expression, or cyclin/CDK complex formation could be documented. We conclude that glucocorticoids may accelerate lung maturation by influencing cell cycle control mechanisms, mainly through impairment of G1 cyclin/CDK complex activation. Glucocorticoids are essential anti-inflammatory molecules widely used in the treatment of a large variety of lung diseases. The early postnatal use of glucocorticoids is often motivated by a positive effect on lung maturation in preterm born babies, who otherwise stand a high risk of developing chronic lung disease also called bronchopulmonary dysplasia. However, as a side effect, it has been demonstrated in a number of animal models that glucocorticoids may impair postnatal lung maturation and growth (1-5).The morphologic descriptions of the effects of glucocorticoids on postnatal lung development have established that the acceleration of alveolar wall thinning and microvascular maturation is associated with a reduction in the outgrowth of new interalveolar septa and, therefore, with an inhibition of alveolar formation (4). These data are consistent with the involvement of glucocorticoids in the processes of cellular differentiation and proliferation (6). In normal situations, the balanced action of endogenous glucocorticoids on both processes results in adequate lung maturation. In situations with increased levels of glucocorticoids, it is likely that this balance is no longer maintained resulting in an impairment in lung development.The observations that glucocorticoid treatment was associated with decreased formation of new alveoli strongly suggests an inhibitory effect of these hormones on cell growth, and, therefore, on cell cycle progression. T...

show abstract

Developmental and Reproductive Toxicity Testing

2016

Drug Safety Evaluation

View full text Add to dashboard Cite

Postnatal lung development and its impairment by glucocorticoids

Cited by 33 publications

References 7 publications

Follow-up Study of a Randomized Controlled Trial of Postnatal Dexamethasone Therapy in Very Low Birth Weight Infants: Effects on Pulmonary Outcomes at Age 8 to 11 Years

Follow-up Study of a Randomized Controlled Trial of Postnatal Dexamethasone Therapy in Very Low Birth Weight Infants: Effects on Pulmonary Outcomes at Age 8 to 11 Years

Impairment of Rat Postnatal Lung Alveolar Development by Glucocorticoids: Involvement of the p21CIP1 and p27KIP1 Cyclin-Dependent Kinase Inhibitors

Developmental and Reproductive Toxicity Testing

Contact Info

Product

Resources

About