Differential effect of dexamethasone and hydrocortisone on alveolar growth in rat pups

Fayon, Michaël; Jouvencel, P.; Carles, Dominique; Choukroun, M.L.; Marthan, Roger

doi:10.1002/ppul.10108

Cited by 18 publications

(10 citation statements)

References 27 publications

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“…However, even though DXM or HCS reduced pulmonary inflammation in our study, that did not protect the lungs from their negative effects in terms of alveolar growth. Fayon et al (19) compared the effect of DXM and HCS on lung growth with a lower DXM dose than we used, and they also found that alveolarization was more markedly impaired by DXM than HCS. Dik et al (30) demonstrated that DXM treatment increased fibroblast proliferation despite apparent down-regulation of inflammation in preterm infants at risk of BPD.…”

Section: Discussionmentioning

confidence: 58%

“…These findings were not in agreement with those reported in rats with no other risk factors for altered lung growth. Thus, Fayon et al (19) found that in rat pups with no risk factors for BPD, both HCS and DXM increased alveolar diameter, and decreased the thickness of the inter-airspace walls. This thinning of the inter-airspace walls due to precocious maturation prior to alveolarization was more marked with DXM than HCS.…”

Section: Discussionmentioning

confidence: 99%

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Effects of Postnatal Dexamethasone or Hydrocortisone in a Rat Model of Antenatal Lipopolysaccharide and Neonatal Hyperoxia Exposure

et al. 2012

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The aim of our study was to investigate the differential effects of dexamethasone (DXM) and hydrocortisone (HCS) on somatic growth and postnatal lung development in a rat model of bronchopulmonary dysplasia (BPD). A rat model of BPD was induced by administering intra-amniotic lipopolysaccharide (LPS) and postnatal hyperoxia. The rats were treated with a 6-day (D1-D6) tapering course of DXM (starting dose 0.5 mg/kg/day), HCS (starting dose 2 mg/kg/day), or an equivalent volume of normal saline. DXM treatment in a rat model of BPD induced by LPS and hyperoxia was also associated with a more profound weight loss compared to control and LPS + O2 groups not exposed to corticosteroid, whereas HCS treatment affected body weight only slightly. Examination of lung morphology showed worse mean cord length in both LPS + O2 + DXM and LPS + O2 + HCS groups as compared to the LPS + O2 alone group, and the LPS + O2 + DXM group had thicker alveolar walls than the LPS + O2 group at day 14. The HCS treatment was not significantly associated with aberrant alveolar wall thickening and retarded somatic growth. The use of postnatal DXM or HCS in a rat model of BPD induced by intra-amniotic LPS and postnatal hyperoxia appeared detrimental to lung growth, but there was less effect in the case of HCS. These findings suggest that effect of HCS on somatic growth and pulmonary outcome may be better tolerated in neonates for preventing and/or treating BPD.

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Section: Discussionmentioning

confidence: 58%

Section: Discussionmentioning

confidence: 99%

Effects of Postnatal Dexamethasone or Hydrocortisone in a Rat Model of Antenatal Lipopolysaccharide and Neonatal Hyperoxia Exposure

et al. 2012

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“…However, high or repeated doses can inhibit postnatal somatic and lung growth (253). During the period of active postnatal alveolarization in rats, glucocorticoids inhibit secondary crest formation, accelerate alveolar wall thinning, decrease alveolar number and surface area (20,(254)(255)(256)(257), diminish replication of fibroblasts, impair the conversion of types II to I pneumocytes (255,258,259), and alter collagen and elastin deposition (149,254,260,261), resulting in a morphologic appearance resembling emphysema. In ferrets, corticosteroid treatment reduces size-corrected airway conductance, suggesting that the central airways are more sensitive to its effect than lung parenchyma (262).…”

Section: Nonmechanical Signals and Mediatorsmentioning

confidence: 99%

Mechanisms and Limits of Induced Postnatal Lung Growth

2004

Am J Respir Crit Care Med

140

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Abnormal DevelopmentClinical syndromes. Syndromes that alter expression of growth factors, cytokines, transcription factors, or extracellular matrix (ECM) proteins provide models to explore mechanisms that control alveolar development. Signals that regulate the saccularto-alveolar morphologic transition are poorly understood, but disrupting lung septation during this transition impairs alveolar formation, resulting in a loss of alveolar surface area (20, 21). There are several syndromes of abnormal lung alveolarization in humans. Trisomy 21 (Down syndrome) is associated with reduced lung volumes, alveolar surface area, fewer alveoli, defective elastin deposition, and vascular abnormalities (22, 23). Leprechaunism, caused by a defect of the insulin/insulin-like growth factor-I receptor, is associated with reduced lung surface areas as well as fewer and larger alveoli (24). Oligohydramnios (25), congenital diaphragmatic hernia (CDH) (26), and intrathoracic mass lesions are all associated with pulmonary hypoplasia caused by the lack of interplay between thoracic expansion and stretch imposed on the lung. Lung hypoplasia in CDH is not just a consequence of mechanical lung compression caused by a hole in the diaphragm but also involves primary developmental defects (27). Prenatal tracheal occlusion markedly increases lung size in some fetuses with severe CDH; however, survival remains poor because of respiratory insufficiency and prematurity (28). After CDH repair, significant postnatal alveolar growth and vascular remodeling are seen (26); long-term survivors show lower lung volumes but normal airway function and exercise tolerance (29), suggesting the occurrence of "catch-up" lung growth once the underlying abnormalities are corrected.By far the most common cause of abnormal postnatal human lung development is bronchopulmonary dysplasia (BPD). Classically, BPD occurs in the preterm infant lung exposed to hyperoxia and mechanical ventilation (30-32), resulting in extensive alveolar fibroproliferation, bronchovascular smooth muscle hyperplasia, and inhibition of distal lung formation leading to longterm pulmonary dysfunction persisting into adolescence and adulthood. The advent of antenatal steroids, postnatal surfactant replacement, and improved intensive care has ushered in the "new BPD," which lacks the severe bronchovascular lesions and interstitial fibrosis but is characterized by abnormal lung development with simplified acinar structure, poorly formed secondary crests, dysmorphic alveolar capillaries, and blunted expression of angiogenic growth factors and their receptors (33-36). There is little information on the pathology of "new BPD" in infants who survive; it remains to be seen whether long-term "catch-up" lung growth occurs in these survivors.

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“…In the present study, the number of alveolar attachments was significantly reduced in both the Bud-and Dex-treated animals; however, this was only the case for airways with a Pi Ͻ 0.75 mm. Similarly, a recent study by Fayon and colleagues (9) reported that the number of alveolar attachments to bronchioles per millimeter of the peribronchial sheath (diameter Ͻ 0.4 mm) was reduced by one-third in Dex-treated rat pups (0.4 g subcutaneous daily between days 4 and 14) compared with controls and hydrocortisone-treated animals. These findings also illustrate the varied effects of different types of glucocorticoids, and it is likely that this variability is dependent on the drug delivery method, dose, and potency.…”

Section: Discussionmentioning

confidence: 66%

Impact of postnatal glucocorticoids on early lung development

Kovar¹,

Willet²,

Hislop³

et al. 2005

Journal of Applied Physiology

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Inhaled glucocorticoid treatment during the first 2 yr of life is controversial because this is a period of major structural remodeling of the lung. Rabbits received aerosolized budesonide (Bud; 250 microg/ml) or injected dexamethasone (Dex; 0.05 mg.ml(-1).kg(-1)) between 1 and 5 wk of age. Treatment with Bud caused specific growth retardation of the lung. Dex but not Bud affected the mechanical properties of the lung parenchyma, when corrected for lung volume. Small peripheral airway walls in both glucocorticoid groups were thinner and had fewer alveolar attachment points with greater distance between attachments than controls, but collagen content was not affected by glucocorticoids. Dex led to reduced body weight, lung volume, alveolar number, and surface area. The alveolar size and number and elastin content, when related to lung volume, was not affected by Bud, suggesting normal structural development but inhibition of total growth. Arterial wall thickness and diameter were affected by Bud. This study demonstrates that developing lungs are sensitive to inhaled glucocorticoids. As such, the use of glucocorticoids in young infants and children should be monitored with caution and only the lowest doses that yield significant clinical improvement should be used.

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Differential effect of dexamethasone and hydrocortisone on alveolar growth in rat pups

Cited by 18 publications

References 27 publications

Effects of Postnatal Dexamethasone or Hydrocortisone in a Rat Model of Antenatal Lipopolysaccharide and Neonatal Hyperoxia Exposure

Effects of Postnatal Dexamethasone or Hydrocortisone in a Rat Model of Antenatal Lipopolysaccharide and Neonatal Hyperoxia Exposure

Mechanisms and Limits of Induced Postnatal Lung Growth

Impact of postnatal glucocorticoids on early lung development

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