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Biomedical subjects

Anne Greenough

Publications and source records attributed to Anne Greenough.

At least 19 recordsLinked to original sources

Improving early diagnosis of bronchopulmonary dysplasia.

INTRODUCTION: Bronchopulmonary disease (BPD) is associated with long-term neurodevelopmental and cardiorespiratory complications, often requiring significant use of resources. To reduce this healthcare burden, it is essential that those at high risk of BPD are identified early so that strategies are introduced to prevent disease progression. Our aim was to discuss potential methods for improving early diagnosis in the first week after birth. AREAS COVERED: A narrative review was undertaken. The search strategy involved searching PubMed, Embase and Cochrane databases from 1967 to 2024. The results of potential biomarkers and imaging modes are discussed. Furthermore, the value of scoring systems is explored. EXPERT OPINION: BPD occurs as a result of disruption to pulmonary vascular and alveolar development, thus abnormal levels of factors regulating those processes are promising avenues to explore with regard to early detection of high-risk infants. Data from twin studies suggests genetic factors can be attributed to 82% of the observed difference in moderate to severe BPD, but large genome-wide studies have yielded conflicting results. Comparative studies are required to determine which biomarker or imaging mode may most accurately diagnose early BPD development. Models which include the most predictive factors should be evaluated going forward.

Humans↗

Temporal relationship of asthma to acute chest syndrome in sickle cell disease.

Acute chest syndrome (ACS) is an important cause of mortality and morbidity in children with sickle cell disease (SCD). An association between asthma and ACS has been reported. Our aims were to determine whether asthma was more common in SCD children than controls and the relationship of the timing of the SCD children's first ACS episode to a diagnosis of asthma. One hundred and sixty-five SCD children median age 8.2 (range 0.3-17.3) years and 151 similar ethnic origin and aged controls were prospectively recruited into the study and a detailed history was taken from all of the children to determine if they were taking anti-asthma medication. The medical records of the SCD children were examined to assess whether they had an ACS episode, the age this episode occurred and when any diagnosis of asthma had been made. A similar proportion of the SCD children and controls were taking anti-asthma medication (7% and 9%). Thirty-three SCD children had at least one ACS episode. More of the children who had an ACS compared to those who had not were taking anti-asthma medication (P = 0.02). The ACS children had been diagnosed as asthmatic at a median of 3.5 (range 0.5-7) years prior to their first ACS episode. In conclusion, these results suggest asthma exacerbations may predispose to ACS episodes.

Acute Disease↗

Lung function and exhaled nitric oxide levels in infants developing chronic lung disease.

Chronic lung disease (CLD) is a common outcome of neonatal intensive care. To determine whether the results of serial exhaled nitric oxide (eNO) measurements during the perinatal period differed between infants who did and did not develop CLD. In addition, we wished to assess whether eNO results were more predictive of CLD development than lung function test results or readily available clinical data (gestational age and birthweight). The patients were 24 infants with a median gestational age of 27 (range 25-31) weeks. Measurements of eNO levels, functional residual capacity (FRC), and compliance of the respiratory system (CRS) were attempted on postnatal days 1, 3, 5, 7, 14, and 28 days. The 12 infants who developed CLD were of significantly lower birthweight and gestational age than the rest of the cohort; in addition, they had lower median FRC (P < 0.02) and CRS (P < 0.02) results, but not higher eNO levels, in the first week after birth. Construction of receiver operator characteristic (ROC) curves demonstrated that the CRS and FRC results on Day 3 were the best predictors of CLD development; the areas under the ROC curves were 0.94 and 0.91, respectively. Early lung function test results, but not eNO levels, are useful in predicting CLD development, but are not significantly better than birthweight.

Birth Weight↗

Survey of sleeping position recommendations for prematurely born infants on neonatal intensive care unit discharge.

INTRODUCTION: Prematurely born infants are at an increased risk of sudden infant death syndrome (SIDS), particularly when sleeping prone. Parents are strongly influenced in their choice of sleeping position for their infant by practitioners. The aim of this study was to determine the neonatal units' recommendations regarding the sleeping position for premature infants prior to and after discharge and ascertain whether there had been changes from those recorded in a survey performed in 2001-2002. MATERIALS AND METHODS: A questionnaire survey was sent to all 229 neonatal units in the United Kingdom; 80% responded. RESULTS AND DISCUSSION: The majority (83%) of units utilized the supine sleep position for infants at least 1-2 weeks prior to discharge, but after discharge, only 38% of the units actively discouraged prone sleeping and 17% additionally recommended side sleeping. Compared to the previous survey, significantly more units started infants with supine sleeping 1-2 weeks prior to discharge (p < 0.0001) and fewer recommended side sleeping after discharge (p = 0.0015). However, disappointingly, less actively discouraged prone sleeping after discharge (p = 0.0001). CONCLUSION: Recommendations regarding sleeping position for prematurely born infants after neonatal discharge by some practitioners remain inappropriate. Evidence-based guidelines are required as these would hopefully inform all neonatal units' recommendations.

Adult↗

Sleeping position, oxygen saturation and lung volume in convalescent, prematurely born infants.

OBJECTIVE: To determine whether the effects of sleeping position on lung volume and oxygenation are influenced by postmenstrual age (PMA) and oxygen dependency in convalescent prematurely born infants. DESIGN: Prospective study. SETTING: Tertiary neonatal unit. PATIENTS: 41 infants (21 oxygen dependent), median gestational age 28 weeks (range 24-31 weeks) and birth weight 1120 g (range 556-1780 g). INTERVENTION: Infants were studied both supine and prone at two-weekly intervals from 32 weeks' PMA until discharge. Each posture was maintained for 1 h. MAIN OUTCOME MEASURES: Pulse oximeter oxygen saturation (Spo(2)) was monitored continuously, and at the end of each hourly period functional residual capacity (FRC) was measured. RESULTS: Overall, lung volumes were higher in the prone position throughout the study period; there was no significant effect of PMA on lung volumes. Overall, Spo(2) was higher in the prone position (p = 0.02), and the effect was significant in the oxygen-dependent infants (p = 0.03) (mean difference in Spo(2) between prone and supine was 1.02%, 95% CI 0.11% to 1.92%), but not in the non-oxygen-dependent infants. There was no significant influence of PMA on Spo(2). CONCLUSION: In the present study, prone sleeping did not improve oxygenation in prematurely born infants, 32 weeks' PMA or older and with no ongoing respiratory problems. However, the infants were monitored in each position for an hour, thus it is recommended that oxygen saturation should continue to be monitored after 32 weeks' PMA to be certain that longer periods of supine sleeping are not associated with loss of lung volume and hypoxaemia.

Functional Residual Capacity↗

A scoring system to predict chronic oxygen dependency.

INTRODUCTION: Chronic oxygen dependency (COD) is a common adverse outcome of very premature birth. It is, therefore, important to develop an accurate and simple predictive test to facilitate targeting of interventions to prevent COD. Our aim was to determine if a simple score based on respiratory support requirements predicted COD development. METHODS: A retrospective study of 136 infants, median gestation age (GA) 28 weeks (range: 23-33 weeks) and a prospective study of 75 infants, median GA 30 weeks (range: 23-32 weeks), were performed. The score was calculated by multiplying the inspired oxygen concentration by the level of respiratory support (mechanical ventilation: 2.5; continuous positive airway pressure: 1.5; nasal cannula or head box oxygen or air: 1.0). Scores were calculated on data from days 2 and 7, and their predictive ability compared to that of the maximum inspired oxygen concentration at those ages and (retrospective study) the results of lung volume measurement. RESULTS: Infants that were oxygen dependent at 28 days and 36 weeks post-menstrual age (PMA) had higher scores on days 2 (p<0.0001, p<0.0001, respectively) and 7 (p<0.0001, p<0.0001, respectively) than the non-oxygen dependent infants in both the retrospective and prospective cohorts. Construction of receiver operator characteristic curves demonstrated the score performed better than the inspired oxygen level and lung volume measurement results. A score on day 7 >0.323 had 95% specificity and 78% sensitivity in predicting COD at 28 days, and 80% specificity and 73% sensitivity in predicting COD at 36 weeks PMA. CONCLUSION: Chronic oxygen dependency can be predicted using a simple scoring system.

Bronchopulmonary Dysplasia↗

Bronchopulmonary dysplasia--long term follow up.

Fifty percent of BPD infants require readmission to hospital during infancy, particularly if they suffer an RSV infection. Many BPD infants require supplementary oxygen at home, early discharge can be achieved if those still requiring nasogastric feeding are given appropriate community support. Troublesome respiratory symptoms are common in children who had BPD, as are lung function abnormalities even in adolescents and young adults.

Bronchopulmonary Dysplasia↗

High frequency oscillation and liquid ventilation.

During high frequency oscillation ventilation (HFOV) small tidal volumes are delivered at fast frequencies, usually between 10 and 15 Hz. Meta-analysis of randomised trials of prophylactic HFOV versus conventional ventilation have demonstrated only a modest reduction in BPD amongst survivors in the HFOV groups. Similarly, no long term advantages of HFOV have been highlighted when it is used as rescue mode, but there have been few randomised studies. During liquid ventilation, the lungs are filled with perfluorocarbon, which, compared to water, has low surface tension and a high solubility for respiratory gases. Clinical experience of liquid ventilation is limited, but improvements in oxygenation and lung function have been shown in short term studies.

Animals↗

Extracellular matrix regulates enhanced eotaxin expression in asthmatic airway smooth muscle cells.

RATIONALE: Altered airway smooth muscle (ASM) function and enrichment of the extracellular matrix (ECM) with fibronectin and collagen are key features of asthma. Previously, we have reported these ECM proteins enhance ASM synthetic function. OBJECTIVE: We compared ASM cultured from endobronchial biopsies from subjects with and without asthma to assess if asthmatic cells were hypersecretory and determined whether the underlying mechanism involved autocrine ECM production. METHODS AND MEASUREMENTS: Cells from subjects with and without asthma were cultured on plastic or in plates precoated with ECM proteins. Cytokine production was evaluated by enzyme-linked immunosorbent assay and by reverse transcriptase-polymerase chain reaction. Function-blocking integrin antibodies were used to identify integrin involvement. RESULTS: Baseline eotaxin and its production after stimulation with interleukin (IL)-13, IL-1beta, or tumor necrosis factor-alpha was increased (2.5- to 6.0-fold) in ASM cells cultured from subjects with asthma compared with healthy subjects. When seeded on ECM from asthmatic ASM, IL-13-dependent eotaxin release from healthy or asthmatic ASM was enhanced compared with culture on healthy ECM. The ECM substrates fibronectin and type I collagen each enhanced IL-13-dependent eotaxin release, and Western immunoblot indicated that fibronectin expression was higher in asthmatic ASM cells. Integrin-blocking antibodies revealed that alpha5beta1 was required for more than 50% of the enhanced IL-13-dependent eotaxin release by ASM cells from subjects with asthma, whereas alpha2beta1 or alphavbeta3 neutralization lacked effect. CONCLUSION: The data indicate that ASM cells cultured from subjects with asthma are hypersecretory compared with cells from healthy donors and that autocrine fibronectin secretion acting via alpha5beta1 in part underlies this effect.

Adult↗

Bronchopulmonary dysplasia.

Bronchopulmonary dysplasia is a chronic lung disease that affects premature babies and contributes to their morbidity and mortality. Improved survival of very immature infants has led to increased numbers of infants with this disorder. This increase puts a heavy burden on health resources since these infants need frequent re-admission to hospital in the first 2 years after birth and, even as adolescents, have lung-function abnormalities and persistent respiratory symptoms. Unlike the original description of the disease in 1967, premature infants can develop chronic oxygen dependency without severe, acute respiratory distress; this "new bronchopulmonary dysplasia" could be the result of impaired postnatal lung growth. Whether such infants subsequently have catch-up lung growth, especially if given corticosteroids postnatally, is unknown. No safe and effective preventive therapy has been identified, but promising new treatments directed either at reducing lung injury or improving lung growth are under study.

Antioxidants↗

Impact of acute chest syndrome on lung function of children with sickle cell disease.

OBJECTIVE: To test the hypothesis that children with sickle cell disease (SCD) who experienced an acute chest syndrome (ACS) hospitalization episode would have worse lung function than children with SCD without ACS episodes. STUDY DESIGN: Forced expiratory volume in 1 second (FEV(1)); forced vital capacity (FVC); FEV(1)/FVC ratio; peak expiratory flow (PEF); forced expiratory flow at 25% (FEF(25)), 50% (FEF(50)), and 75% (FEF(75)) of FVC; airway resistance (Raw); and lung volumes were compared in 20 children with ACS and 20 aged-matched children without ACS (median age, 11 years; range, 6 to 16 years). Fourteen age-matched pairs were assessed before and after bronchodilator use. RESULTS: The mean Raw (P = .03), TLC (P = .01), and RV (P = .003) were significantly higher in the group with ACS than in the group without ACS. There were no significant differences in the changes in lung function test results in response to bronchodilator administration between the 2 groups, but the children with ACS had a lower FEF(25) (P = .04) and FEF(75) (P = .03) pre-bronchodilator use and a lower mean FEV(1)/FVC ratio (P = .03) and FEF(75) (P = .03) post-bronchodilator use. CONCLUSIONS: Children with SCD who experienced an ACS hospitalization episode had significant differences in lung function compared with those who did not experience ACS episodes. Our results are compatible with the hypothesis that ACS episodes predispose children to increased airway obstruction.

Acute Disease↗

Absence of the ductus venosus.

Absence of the ductus venosus is a rare vascular anomaly, but clinicians should be aware that it can be diagnosed antenatally and the prognosis is dependent on the type of associated malformation of the fetal vascular system. Antenatal detection of a single umbilical artery and unexplained cardiomegaly should prompt detailed examination of the umbilical and portal veins. Absent ductus venosus is associated with three main patterns of abnormal venous circulation, the worst prognosis being seen when the umbilical vein bypasses the liver and connects to the right atrium. Fetuses with absence of the ductus venosus are at risk of other congenital anomalies including facial clefts, hemivertebrae, cardiac, genitourinary, gastrointestinal anomalies; affected infants also have a poorer prognosis. In conclusion, fetuses with features suggestive of absence of ductus venosus require referral to a tertiary perinatal center.

Esophageal Atresia↗

Effect of prone and supine position on sleep, apneas, and arousal in preterm infants.

OBJECTIVE: Prematurely born compared with term born infants are at increased risk of sudden infant death syndrome, particularly if slept prone. The purpose of this work was to test the hypothesis that preterm infants with or without bronchopulmonary dysplasia being prepared for neonatal unit discharge would sleep longer and have less arousals and more central apneas in the prone position. METHODS: This was a prospective observational study in a tertiary NICU. Twenty-four infants (14 with bronchopulmonary dysplasia) with a median gestational age of 27 weeks were studied at a median postconceptional age of 37 weeks. Video polysomnographic recordings of 2-channel electroencephalogram, 2-channel electro-oculogram, nasal airflow, chest and abdominal wall movements, limb movements, electrocardiogram, and oxygen saturation were made in the supine and prone positions, each position maintained for 3 hours. The duration of sleep, sleep efficiency (total sleep time/total recording time), and number and type of apneas, arousals, and awakenings were recorded. RESULTS: Overall, in the prone position, infants slept longer, had greater sleep efficiency (89.5% vs 72.5%), and had more central apneas (median: 5.6 vs 2.2), but fewer obstructive apneas (0.5 vs 0.9). The infants had more awakenings (9.7 vs 3.5) and arousals per hour (13.6 vs 9.0) when supine. There were similar findings in the bronchopulmonary dysplasia infants. CONCLUSIONS: Very prematurely born infants studied before neonatal unit discharge sleep more efficiently with fewer arousals and more central apneas in the prone position, emphasizing the importance of recommending supine sleeping after neonatal unit discharge for prematurely born infants.

Arousal↗

Problems in the measurement of functional residual capacity.

Accurate assessment of lung volume in infancy is important to determine the impact of disease and the efficacy of therapies. A new generation of infant plethysmographs with lower apparatus deadspace has been produced, but gives lower volume results than those from older traditional plethysmographs. We hypothesized that the new plethysmographs might have greater sensitivity to the adiabatic effect and hence they, rather than the traditional plethysmographs, produced erroneous results. Our aim was to assess the influence of the adiabatic effect on the results of a contemporary plethysmograph, an older traditional plethysmograph and a helium gas dilution system using a lung model. Altering the amount of copper wool within the lung model allowed the influence of the adiabatic effect on the plethysmographic results to be assessed. The measured compared to the actual volumes were significantly lower for the contemporary plethysmograph compared to the traditional plethysmograph (p < 0.001) and to the helium gas dilution system (p < 0.001). Under optimal testing conditions the contemporary plethysmograph under-recorded by 11-13%, whereas the other two systems gave similar results to the actual volumes. As the effect of the adiabatic effect was increased, the discrepancy between the results of the contemporary and the traditional plethysmographs increased. We conclude, the contemporary plethysmograph is more sensitive to adiabatic effects and hence under-records.

Functional Residual Capacity↗

Optimal strategies for newborn ventilation--a synthesis of the evidence.

A variety of ventilation modes are available for the newborn. Although, there have been randomised trials assessing certain modes, these have generally only included prematurely born infants with RDS or infants with severe respiratory failure. Meta-analysis of the results of those trials has demonstrated that neither patient triggered nor high frequency oscillatory ventilation is advantageous for the prematurely born infant with RDS, but extracorporeal membrane oxygenation increases survival in infants with severe respiratory failure. Appropriately designed studies are required to determine the role of newer ventilation modes and whether forms of respiratory support avoiding intubation are less injurious to the lungs. Research should also focus on infants with other respiratory disorders, particularly BPD. Prior to further randomised trials being undertaken, it is essential that the optimum method of applying each ventilator mode is identified and it is clearly understood whether differences in ventilator/oscillator performance influence outcome.

Bronchopulmonary Dysplasia↗

Lung volumes in infants who had mild to moderate bronchopulmonary dysplasia.

"New" bronchopulmonary dysplasia (BPD) has been suggested to be a maldevelopment sequence with reduced alveolarisation of the lungs; affected infants then would be predicted to have low lung volumes. The aim of this study was to test that hypothesis by comparing the lung volumes of infants who had had mild-moderate BPD with those without BPD of similar postmenstrual age. Lung volumes of 17 infants who had mild-moderate BPD (oxygen dependent beyond 28 days, but not past term) (BPD infants) were compared to those of 17 infants without BPD (non-BPD infants). All were born at less than 33 weeks of gestation and studied at postmenstrual ages of 33 to 39 weeks. Lung volume was assessed by measurement of functional residual capacity (FRC). The BPD infants had lower lung volumes (median 19.1 ml/kg) than the non-BPD infants (median 26.5 ml/kg) (p = 0.0001). The BPD compared to the non-BPD infants were of greater postnatal age (p = 0.0003), born at a lower gestational age (p = 0.0001) and of lighter birthweight (p = 0.0001). Regression analysis, however, demonstrated that lung volume was significantly related to BPD status (p = 0.005), independently of postnatal age, birthweight and gestational age. It is concluded that the lower lung volumes of the infants who had had mild-moderate BPD support the hypothesis that new BPD is associated with poor alveolarisation.

Birth Weight↗