Respiratory health in pre-school and school age children following extremely preterm birth

Hennessy, Enid; Bracewell, Melanie A.; Wood, Nicholas; Wolke, Dieter; Costeloe, Kate; Gibson, Alan T.; Marlow, Neil

doi:10.1136/adc.2008.140830

Cited by 134 publications

(108 citation statements)

References 29 publications

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“…Up to 50% of BPD infants require rehospitalization in the first year of life (44)(45)(46)(47). Infants who required home oxygen therapy are at highest risk for rehospitalizations (45,48). Respiratory symptoms, primarily chronic cough and wheezing, a Data are presented as the mean Ϯ standard deviation of the log-transformed cytokine concentration (in pg/ml) and of the change in cytokine concentration between baseline (predose) and 2 and 4 days post-last dose.…”

Section: Discussionmentioning

confidence: 99%

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Pharmacokinetics, Microbial Response, and Pulmonary Outcomes of Multidose Intravenous Azithromycin in Preterm Infants at Risk for Ureaplasma Respiratory Colonization

Merchan

Hassan

Terrin

et al. 2015

Antimicrob Agents Chemother

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The study objectives were to refine the population pharmacokinetics (PK) model, determine microbial clearance, and assess short-term pulmonary outcomes of multiple-dose azithromycin treatment in preterm infants at risk for Ureaplasma respiratory colonization. Fifteen subjects (7 of whom were Ureaplasma positive) received intravenous azithromycin at 20 mg/kg of body weight every 24 h for 3 doses. Azithromycin concentrations were determined in plasma samples obtained up to 168 h post-first dose by using a validated liquid chromatography-tandem mass spectrometry method. Respiratory samples were obtained predose and at three time points post-last dose for Ureaplasma culture, PCR, antibiotic susceptibility testing, and cytokine concentration determinations. Pharmacokinetic data from these 15 subjects as well as 25 additional subjects (who received either a single 10-mg/kg dose [n ‫؍‬ 12] or a single 20-mg/kg dose [n ‫؍‬ 13]) were analyzed by using a nonlinear mixed-effect population modeling (NONMEM) approach. Pulmonary outcomes were assessed at 36 weeks post-menstrual age and 6 months adjusted age. Bronchopulmonary dysplasia (BPD) is the major pulmonary morbidity in infants born preterm and is characterized by arrested alveolar development and chronic inflammation. Studies of human infants and experimental animal models indicate that the central event in BPD pathogenesis is the interruption of normal developmental signaling during early stages of lung development by lung injury that may be initiated in utero by intrauterine infection with a subsequent dysregulated inflammatory response (1-3). A recent meta-analysis of 39 studies confirmed that respiratory tract colonization with the genital mycoplasma species Ureaplasma parvum and Ureaplasma urealyticum increased the risk for development of BPD in extremely low gestation infants (4). It has not been established whether eradicating Ureaplasma spp. from the respiratory tract of preterm infants prevents or attenuates Ureaplasma infection-mediated lung injury.Azithromycin, an azalide antibiotic, has anti-inflammatory properties and antimicrobial activity against Ureaplasma spp. in in vitro (5, 6) and in in vivo experimental models (7-9). Although the efficacies of azithromycin and a related macrolide, clarithromycin, to prevent BPD have been assessed in single-center studies of preterm infants (10-13), the optimal dosing regimens for these antibiotics have not been determined in pharmacokinetics (PK) and pharmacodynamic studies, and the impacts on long-term pulmonary and neurologic outcomes are unknown. Our first steps to address these questions have been to conduct studies in the at-risk population to determine the optimal dose, safety, and in vivo anti-infective efficacy of azithromycin in preparation for future phase III randomized, placebo-controlled trials (14, 15). We previously characterized the PK of a single dose of intravenous (i.v.) azithromycin (10 or 20 mg/kg of body weight) in preterm infants (14). We demonstrated both doses were safe in infants who

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Section: Discussionmentioning

confidence: 99%

“…Maternal smoking during pregnancy and smoking in the home also contribute to adverse respiratory outcomes in preterm infants (48). Ureaplasma respiratory tract colonization has been proposed as an etiologic factor in reactive airway disease in young infants.…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics, Microbial Response, and Pulmonary Outcomes of Multidose Intravenous Azithromycin in Preterm Infants at Risk for Ureaplasma Respiratory Colonization

Merchan

Hassan

Terrin

et al. 2015

Antimicrob Agents Chemother

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“…They continue to have increased sensitivity to environmental stimuli, such as cigarette smoke, and to viral infections (45,46), with enhanced inflammation and bronchoconstriction. Persistent, resident mast cells have been associated with similar symptoms in patients with asthma.…”

Section: Discussionmentioning

confidence: 99%

Genome-Wide Transcriptional Profiling Reveals Connective Tissue Mast Cell Accumulation in Bronchopulmonary Dysplasia

Bhattacharya¹,

Go²,

Krenitsky³

et al. 2012

Am J Respir Crit Care Med

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Rationale: Bronchopulmonary dysplasia (BPD) is a major complication of premature birth. Risk factors for BPD are complex and include prenatal infection and O 2 toxicity. BPD pathology is equally complex and characterized by inflammation and dysmorphic airspaces and vasculature. Due to the limited availability of clinical samples, an understanding of the molecular pathogenesis of this disease and its causal mechanisms and associated biomarkers is limited. Objectives: Apply genome-wide expression profiling to define pathways affected in BPD lungs. Methods: Lung tissue was obtained at autopsy from 11 BPD cases and 17 age-matched control subjects without BPD. RNA isolated from these tissue samples was interrogated using microarrays. Standard gene selection and pathway analysis methods were applied to the data set. Abnormal expression patterns were validated by quantitative reverse transcriptase-polymerase chain reaction and immunohistochemistry. Measurements and Main Results: We identified 159 genes differentially expressed in BPD tissues. Pathway analysis indicated previously appreciated (e.g., DNA damage regulation of cell cycle) as well as novel (e.g., B-cell development) biological functions were affected. Three of the five most highly induced genes were mast cell (MC)-specific markers. We confirmed an increased accumulation of connective tissue MC TC (chymase expressing) mast cells in BPD tissues. Increased expression of MC TC markers was also demonstrated in an animal model of BPD-like pathology.Conclusions: We present a unique genome-wide expression data set from human BPD lung tissue. Our data provide information on gene expression patterns associated with BPD and facilitated the discovery that MC TC accumulation is a prominent feature of this disease. These observations have significant clinical and mechanistic implications.

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“…Again, variable definitions of BPD were used. The majority of studies (n = 26) used case-control study design (18,19,22,23,25,28,29,32,34,35,37,39,41,42,44,45,54,56,59,62,63,66,67,70,71,75), and the remaining used either retrospective (n = 4) or prospective (n = 4) cohort study designs (20,24,36,43,49,52,57,60).…”

Section: N = 90mentioning

confidence: 99%

Understanding the Short- and Long-Term Respiratory Outcomes of Prematurity and Bronchopulmonary Dysplasia

Islam¹,

Keller

Aschner

et al. 2015

Am J Respir Crit Care Med

274

229

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Bronchopulmonary dysplasia (BPD) is a chronic respiratory disease associated with premature birth that primarily affects infants born at less than 28 weeks' gestational age. BPD is the most common serious complication experienced by premature infants, with more than 8,000 newly diagnosed infants annually in the United States alone. In light of the increasing numbers of preterm survivors with BPD, improving the current state of knowledge of long-term respiratory morbidity for infants with BPD is a priority. We undertook a comprehensive review of the published literature to analyze and consolidate current knowledge of the effects of BPD that are recognized at specific stages of life, including infancy, childhood, and adulthood. In this review, we discuss both the short-term and long-term respiratory outcomes of individuals diagnosed as infants with the disease and highlight the gaps in knowledge needed to improve early and lifelong management of these patients.Keywords: bronchopulmonary dysplasia; respiratory outcomes; preterm birth At a Glance CommentaryScientific Knowledge on the Subject: Currently, there is no comprehensive review of what is known about the short-and long-term respiratory morbidity associated with prematurity and bronchopulmonary dysplasia (BPD). With contemporary improvements in treatment and technology, more infants born prematurely are surviving with poorly understood respiratory sequelae that will present unique challenges to pediatric and ultimately adult pulmonary providers.What This Study Adds to the Field: This review provides both clinicians and researchers with a comprehensive understanding of the range of pulmonary outcomes for survivors of BPD. In reviewing the literature, we have also summarized the research gaps in this field.The significant associations of preterm birth with adult health have become increasingly recognized through epidemiological research and clinical observations (1-3). Complications of preterm birth (,37 completed weeks of gestation) are most often seen in very preterm infants (28-31 wk gestation) and extremely preterm infants (,28 wk gestation) (4), although it is increasingly recognized that even modestly preterm infants are at increased risk of adverse health and developmental outcomes.Preterm birth predisposes individuals to the development of chronic respiratory disease in adulthood, including asthma and chronic obstructive pulmonary disease (COPD) (5). Worldwide, it has been estimated that more than 15 million babies (11% of live births) are born preterm. Health complications associated with preterm birth have recently been implicated as the cause of 36% (1.03 million) of neonatal deaths. Rates of preterm birth are increasing in most countries with reliable

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Respiratory health in pre-school and school age children following extremely preterm birth

Abstract: Extremely preterm children have a continuum of poor respiratory health over the first 6 years, which is exacerbated by smoking during pregnancy and in the home.

Cited by 134 publications

References 29 publications

Pharmacokinetics, Microbial Response, and Pulmonary Outcomes of Multidose Intravenous Azithromycin in Preterm Infants at Risk for Ureaplasma Respiratory Colonization

Pharmacokinetics, Microbial Response, and Pulmonary Outcomes of Multidose Intravenous Azithromycin in Preterm Infants at Risk for Ureaplasma Respiratory Colonization

Genome-Wide Transcriptional Profiling Reveals Connective Tissue Mast Cell Accumulation in Bronchopulmonary Dysplasia

Understanding the Short- and Long-Term Respiratory Outcomes of Prematurity and Bronchopulmonary Dysplasia

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