Deletion Allele of Angiotensin-Converting Enzyme is Associated with Increased Risk and Severity of Bronchopulmonary Dysplasia

Kazzi, S. Nadya J.; Quasney, Michael W.

doi:10.1016/j.jpeds.2005.07.029

Cited by 46 publications

(37 citation statements)

References 45 publications

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“…The persistence of airway obstruction in these children is likely multifactorial in nature, potentially reflecting the impact of preterm birth per se (48,49), the vulnerability of the extremely immature lung even to low ventilatory pressures or oxygen concentrations, increased airway compliance and/or disruption of the collagen infrastructure with fewer alveolar attachments and decreased pulmonary elastic recoil (44,(50)(51)(52), and/or reprogramming of key innate immunoregulatory pathways in the lung in response to neonatal hyperoxia (53). Despite the marked differences in subsequent outcome, prenatal and neonatal characteristics were remarkably similar between those who did and did not develop BPD, possibly reflecting variance in genetic susceptibility to BPD (54,55). The implications of the potential undertreatment of lung disease in children born preterm have been discussed (29,56).…”

Section: Discussionmentioning

confidence: 99%

Lung Function and Respiratory Symptoms at 11 Years in Children Born Extremely Preterm

Fawke¹,

Lum²,

Kirkby³

et al. 2010

Am J Respir Crit Care Med

486

386

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Rationale: The long-term respiratory sequelae of infants born extremely preterm (EP) and now graduating from neonatal intensive care remains uncertain. Objectives: To assess the degree of respiratory morbidity and functional impairment at 11 years in children born EP (i.e., at or less than 25 completed weeks of gestation) in relation to neonatal determinants and current clinical status. Methods: Pre-and postbronchodilator spirometry were undertaken at school in children born EP and classroom control subjects. Physical examination and respiratory health questionnaires were completed. Multivariable regression was used to estimate the predictive power of potential determinants of lung function. Measurements and Main Results: Spirometry was obtained in 182 of 219 children born EP (129 with prior bronchopulmonary dysplasia ½BPD) and 161 of 169 classmates, matched for age, sex, and ethnic group. Children born EP had significantly more chest deformities and respiratory symptoms than classmates, with twice as many (25 vs. 13%; P , 0.01) having a current diagnosis of asthma. Baseline spirometry was significantly reduced (P , 0.001) and bronchodilator responsiveness was increased in those born EP, the changes being most marked in those with prior BPD. EP birth, BPD, current symptoms, and treatment with b-agonists are each associated independently with lung function z-scores (adjusted for age, sex, and height) at 11 years. Fifty-six percent of children born EP had abnormal baseline spirometry and 27% had a positive bronchodilator response, but less than half of those with impaired lung function were receiving any medication. Conclusions: After extremely preterm birth, impaired lung function and increased respiratory morbidity persist into middle childhood, especially among those with BPD. Many of these children may not be receiving appropriate treatment.

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Section: Discussionmentioning

confidence: 99%

Lung Function and Respiratory Symptoms at 11 Years in Children Born Extremely Preterm

Fawke¹,

Lum²,

Kirkby³

et al. 2010

Am J Respir Crit Care Med

486

386

View full text Add to dashboard Cite

show abstract

“…interleukin-6 or 13), or deficiency in Toll-like receptor 4, which is a critical receptor component for gram-negative bacteria's lipopolysaccharide inflammatory response, show increased susceptibility to hyperoxia-induced lung injury. [19][20][21][22][23] In humans, polymorphisms in surfactant protein A & B, TNF-α, angiotensin-converting enzyme and gluthathione-S-transferase-P1 genes, genes, and having known altered biological functions, have been linked in small studies with variations in risk of BPD or its severity, [24][25][26][27] although others have failed to show similar associations in independent populations. 28,29 PDA persistence was also largely heritable in our analysis, a finding that is consistent with a significant contribution of individual's ethnic background to susceptibility.…”

Section: Discussionmentioning

confidence: 99%

Heritability of Bronchopulmonary Dysplasia, Defined According to the Consensus Statement of the National Institutes of Health

2008

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Objective-The goal was to determine the magnitude of genetic effects on susceptibility and risk factors for bronchopulmonary dysplasia by using the clinically validated National Institutes of Health consensus definition as a demonstrated proxy for long-term respiratory and neurodevelopmental outcomes in extremely low birth weight infants.Methods-We analyzed clinical data from twin pairs born at ≤30 completed weeks gestation in British Columbia, Canada, between 1993 and 2006. Differences in correlations between monozygotic (MZ) and dizygotic (DZ) twin pairs and model-fitting approaches were used to quantify the relative contribution of genetic, shared environmental and non-shared environmental effects.Results-Among 318 twins of known zygosity, monozygotic twin pair similarities were greater than those observed for dizygotic pairs, which suggest significant heritability for bronchopulmonary dysplasia. Model-fitting analyses confirmed that genetic effects accounted for 82% and 79% of the observed variance in bronchopulmonary dysplasia susceptibility, defined on the basis of the need for supplemental oxygen at 36 weeks or the National Institutes of Health consensus definition, respectively. Variations in rates of hemodynamically significant PDA were largely accounted for by genetic effects, whereas variance in susceptibility to blood-borne bacterial infections was largely attributable environmental factors both common and unique to each infant.Conclusions-Susceptibility to BPD and persistence of PDA are both significantly heritable. Our study strengthens the case for investigating further genetic risk stratification markers useful for predicting the most significant long-term respiratory and neurodevelopmental consequences of bronchopulmonary dysplasia in premature neonates.

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“…(a) genetic predisposition, including sex, race 27,28 and the effect of various genetic polymorphisms, such as those associated with the b2 adrenoceptor, Angiotensin Converting Enzyme (ACE) and glutathione S transferase alleles, [29][30][31][32] (b) preterm delivery per se, [33][34][35] (c) neonatal respiratory disorders and the various treatment strategies on the growing and differentiating lung, [1][2][3][4]27,[36][37][38][39][40] and (d) interactions between neonatal lung disease and the environment (including exposure to tobacco smoke, allergens and infections). 15,41 This in turn requires international consensus on which essential details should be recorded for infants recruited to such studies.…”

Section: The Next Steps?mentioning

confidence: 99%

Lung function in infants and young children with chronic lung disease of infancy: The next steps?

Stocks

Coates

Bush

2006

Pediatric Pulmonology

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Summary. Over the past year, a series of papers have reviewed the literature concerning assessment and interpretation of lung function in infants and young children with chronic lung disease of infancy. This manuscript, which represents the final paper in that series, summarizes the findings to date and highlights key areas for future research. Despite the huge literature in this field, interpretation of results and their use in guiding clinical management are still limited by difficulties in 'normalizing data' according to body size and maturation and selection of appropriate control groups. Furthermore, sensitive tests that more closely reflect the underlying pathophysiology of 'new' bronchopulmonary dysplasia, together with simple and reliable methods of assessing lung maturity at birth and true oxygen requirements at specified time points are urgently required. Research in this field is also challenged by the need to separate the independent effects of genetic predisposition, gene-environment interactions, preterm delivery, neonatal respiratory disorders and various treatment strategies on the growing lung. The extent to which disruption of lung growth following premature exposure to the extra-uterine environment leads to an earlier or more aggravated decline in respiratory function in later adult life remains to be elucidated. Whatever its origin, given the increasing survival of smaller and more immature infants, the long term sequelae of neonatal lung disease, are likely to continue to change, requiring ongoing, carefully designed longitudinal studies. Future research strategies need to encompass a multicenter, multidisciplinary, collaborative approach with closer links between clinicians and basic scientists, to ensure that the most relevant research questions are addressed using appropriate methodology and that findings are implemented into clinical practice in a more timely fashion. Pediatr Pulmonol.

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Deletion Allele of Angiotensin-Converting Enzyme is Associated with Increased Risk and Severity of Bronchopulmonary Dysplasia

Cited by 46 publications

References 45 publications

Lung Function and Respiratory Symptoms at 11 Years in Children Born Extremely Preterm

Lung Function and Respiratory Symptoms at 11 Years in Children Born Extremely Preterm

Heritability of Bronchopulmonary Dysplasia, Defined According to the Consensus Statement of the National Institutes of Health

Lung function in infants and young children with chronic lung disease of infancy: The next steps?

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