Chronic Lung Disease Of Infancy Research Articles

Palivizumab prophylaxis of respiratory syncytial virus disease in 2000-2001: results from The Palivizumab Outcomes Registry.

The objective of the Registry was to characterize the population of infants receiving prophylaxis for respiratory syncytial virus (RSV) disease by describing the patterns and scope of usage of palivizumab in a cross section of US infants. RSV hospitalization outcomes were also described. The Palivizumab (Synagis, MedImmune, Inc., 25 West Watkins Mill Road, Gaithersburg, MD 20878) Outcomes Registry was a prospective multicenter survey conducted at 63 sites. Demographics, injection history, and RSV hospitalization outcomes were collected on 2,116 infants receiving palivizumab. Infants were enrolled in the Registry between September 1, 2000-March 1, 2001, at the time of their first injection. Infants born at less than 32 weeks of gestation accounted for 47% of infants enrolled, and those between 32-35 weeks accounted for 45%; approximately 8% were greater than 35 weeks of gestation. Lower RSV hospitalization rates were observed in infants who had greater adherence to regularly scheduled injections. Nearly one-half of all hospitalizations occurred within the first and second injection intervals, suggesting the importance of early RSV protection. The confirmed RSV hospitalization rate of all infants in the Registry was 2.9%; the rate was 5.8% in infants with chronic lung disease of infancy, and 2.1% in premature infants without chronic lung disease. In conclusion, these data support the continued effectiveness of palivizumab prophylaxis for severe RSV lower respiratory tract disease in a large cohort of high-risk infants from geographically diverse pediatric offices and clinics. The Palivizumab Outcomes Registry provides an opportunity to assess palivizumab utilization and clinical effectiveness in the US.

Prophylactic high-frequency oscillatory ventilation in preterm infants.

The role of high-frequency oscillatory ventilation (HFOV) for the treatment of respiratory disease in preterm infants remains uncertain. Several randomized trials, comparing HFOV and conventional ventilation (CV) have been performed and their results suggest that HFOV may reduce the incidence of chronic lung disease (CLD) in preterm infants. However, the trials have several limitations and it remains unclear whether HFOV might increase intracranial pathology in very prematurely born infants. UKOS, a large, UK-based, multicentre trial was conducted to establish conclusively the role of prophylactic HFOV for the prevention of CLD in infants born prior to 29 wk of gestational age. There is still a need to fully evaluate prophylactic HFOV with particular emphasis on both short and long term respiratory and neurological outcomes.

Leukemoid reaction and chronic lung disease in infants with very low birth weight

Leukemoid reaction and chronic lung disease in infants with very low birth weight

Bronchopulmonary dysplasia (chronic lung disease of infancy): an update for the pediatrician.

This paper is a review of the changes that have occurred over the past 35 years in the clinical and radiologic presentation of bronchopulmonary dysplasia (BPD), now more commonly referred to as chronic lung disease of infancy (CLD). Curent thoughts on etiology are only briefly discussed. The major focus is the management of the patient with CLD by the primary care physician once the patient has been discharged from hospital. Oxygen, diuretic, bronchodilator, antiinflammatory and nutritional therapies are discussed in detail. Finally, current information on long-term prognosis and recommendations for the prevention of RSV and influenza infections are reviewed.

Postnatal corticosteroids to treat or prevent chronic lung disease in preterm infants.

This statement is intended for health care professionals caring for neonates and young infants. The objectives of this statement are to review the short- and long-term effects of systemic and inhaled postnatal corticosteroids for the prevention or treatment of evolving or established chronic lung disease and to make recommendations for the use of corticosteroids in infants with very low birth weight. The routine use of systemic dexamethasone for the prevention or treatment of chronic lung disease in infants with very low birth weight is not recommended.

Postnatal corticosteroids to treat or prevent chronic lung disease in preterm infants

This statement is intended for health care professionals caring for neonates and young infants. The objectives of this statement are to review the short and long term effects of systemic and inhaled postnatal corticosteroids for the prevention or treatment of evolving or established chronic lung disease, and to make recommendations for the use of corticosteroids in infants with very low birth weight. The routine use of systemic dexamethasone for the prevention or treatment of chronic lung disease in infants with very low birth weight is not recommended.

Leukemoid reaction and chronic lung disease in infants with very low birth weight

Objectives: To analyze the relationship between the leukemoid reaction and chronic lung disease in very-low-birth-weight (VLBW) infants.Methods: Neonates born weighing less than 1500g without evidence of congenital anomalies and admitted to our hospital from October 1985 to December 1999 comprised our study. Leukemoid reaction was defined as a peripheral white blood cell (WBC) countof ≥ 50 × 103/μl. The infants who demonstrated a leukemoid reaction formed the study group, while the remainder formed the control group. The relationship between neonatal variablesand WBC counts was studied.Results: Fourteen of the 486 infants demonstrated WBC counts of ≥ 50 × 103/μl, with an incidence of 2.9%. Univariate analysis demonstrated asignificant association between a leukemoid reaction and chronic lung disease following intrauterine infection.Conclusion: A leukemoid reaction was observed in 2.9% of VLBW infants in our neonatalintensive care unit. A significant association was demonstrated between the leukemoid reaction and chronic lung disease following intrauterine infection.

Neonatal dexamethasone treatment induces long-lasting changes in T-cell receptor Vβ repertoire in rats

Glucocorticoids are frequently administered for the prevention of chronic lung disease in infants with respiratory distress syndrome. However, neonatal treatment may have consequences for immune functioning in the long-term. Here we demonstrate that neonatal glucocorticoid treatment has long-lasting effects on mRNA expression of several Vβ genes within the CD4 and CD8 T cell subset in rats. Changes in the peripheral T cell Vβ repertoire may be a consequence of altered intrathymic selection events in which corticosterone plays an important role. Indeed, here we show that neonatal glucocorticoid treatment affects corticosterone production by thymic epithelial cells during neonatal life. In conclusion, changes in T cell Vβ repertoire after neonatal glucocorticoid treatment may contribute to altered immune reactivity in later life.

Effectiveness of palivizumab: evaluation of outcomes from the 1998 to 1999 respiratory syncytial virus season. The Palivizumab Outcomes Study Group.

Respiratory syncytial virus (RSV) remains a significant cause of morbidity, especially in premature infants and immunocompromised children, resulting in approximately 100 000 hospitalizations annually. A study was performed to evaluate the outcomes of those given palivizumab (Synagis; MedImmune, Inc., Gaithersburg, MD) during the 1998 to 1999 RSV season, its first season in general use. A retrospective chart review of 1839 patients from 9 United States sites was conducted, representing all patients given palivizumab at each site. Those evaluated were to have a gestational age of < or =35 weeks, were to be <2 years old at their first injection and were to have received at least one dose of palivizumab (humanized monoclonal antibody against RSV) between September, 1998, and May, 1999. Gestational age, comorbidities, frequency of injections, hospitalizations and length of hospital stays were assessed. The antigen- or culture-positive RSV hospitalization rates for those given prophylaxis were 2.3% (42 of 1839) overall, 16/399 (4.0%) with chronic lung disease of infancy and 26 of 1227 (2.1%) born prematurely without chronic lung disease of infancy. Twenty-six patients had a gestational age of >35 weeks and were included in the analysis. Only 2.3% of children receiving palivizumab prophylaxis were hospitalized with RSV lower respiratory infection. This compares favorably with the rates observed in the pivotal trial (IMpact-RSV trial in 1996 to 1997), in which prophylaxis reduced hospitalization from 10.6% in the placebo group to 4.8% in those children receiving prophylaxis.

Ureaplasma urealyticum and its association with chronic lung disease in Asian neonates

The aim of the present prospective cohort study was to evaluate the relationship between lower respiratory tract colonization with Ureaplasma urealyticum and development of chronic lung disease (CLD) in a high-risk neonatal population. Prospective cohort study of preterm infants with a birthweight < 1,500 g needing mechanical ventilation within 24 h of birth in a tertiary care neonatal unit. Endotracheal aspirates from these infants were cultured within 24 h for U. urealyticum and the rate of colonization was determined. The primary outcome measure was the incidence of CLD at 28 days of life. Of the 41 infants studied, 10 (24%) infants were colonized with U. urealyticum. The colonization rate was higher in babies < 1,000 g compared with babies weighing 1,000-1,500 g (P = 0.04). There was no significant difference between the colonized and non-colonized groups with regard to the antenatal use of steroids, maternal prolonged rupture of membranes, gestational age, birthweight, sex, respiratory distress syndrome, use of surfactant, patent ductus arteriosus and gastrooesophageal reflux. Of the 37 survivors, 20 (54%) developed CLD; eight infants (88.5%) in the colonized group developed CLD compared with 12 infants (42.8%) in the non-colonized group (P = 0.01). Neonates colonized with U. urealyticum were twice as likely to have CLD than non-colonized babies (relative risk 2.01; 95% confidence interval 1.27-3.37). These data suggest a significant association between colonization with U. urealyticum and CLD in infants weighing < 1,500 g.

Vitamin A supplementation in very low birth weight neonates: rationale and evidence.

Bronchopulmonary dysplasia (BPD) is the most prevalent form of chronic lung disease in infancy. Among the 3.9 million births in the United States in 1997, approximately 55 000 newborn infants weighed <1500 g at birth.1 Among these very low birth weight (VLBW) infants, 49 000 infants would be expected to be discharged alive at the end of their first hospitalization (Vanderbilt experience 1998). At an estimated incidence of 24% among the VLBW survivors (Vanderbilt experience 1998), 12 000 new cases of BPD would be expected to emerge annually, making BPD the leading cause of chronic lung disease in infancy. The pathogenesis of BPD involves factors causing injury to an immature lung and factors inhibiting its healing.2,,3 The lung injury can result from such insults as hyaline membrane disease, barotrauma or volutrauma from mechanical ventilation, oxygen toxicity, and airway infection associated with prolonged tracheal intubation.4 The lung healing can be influenced by nutrients, antioxidants, inflammatory cells, eicosanoids, growth factors, peptide hormones, and components of extracellular matrix.5 The role of the essential micronutrient vitamin A (retinol) in the promotion of orderly growth and differentiation of regenerating epithelial tissues makes vitamin A an important nutrient during recovery from lung injury.6,,7 This review focuses on the pathophysiology of vitamin A deficiency in relation to BPD, examines the evidence for vitamin A deficiency in VLBW neonates, and provides guidelines for vitamin A supplementation as an approach toward amelioration of lung disease among the VLBW survivors. Vitamin A promotes normal growth and differentiation of epithelial cells. Vitamin A deficiency, therefore, affects various organ systems, including the lung.6 The histopathologic changes in the respiratory system generally precede other consequences of vitamin A deficiency involving the genitourinary system, eye, and skin.6 Vitamin A deficiency results in a progressive sequence of …

Neonatal chronic lung disease in extremely immature baboons.

A borderline viability model of bronchopulmonary dysplasia (BPD)/chronic lung disease of infancy (CLD) with pathophysiologic parameters consistent with those in extremely immature humans with BPD/CLD is described. After prenatal steroid treatment of pregnant dams, 12 premature baboons were delivered by cesarean-section at 125 d (term gestation, 185 d), treated with exogenous surfactant, and maintained on appropriate oxygen and positive pressure ventilation for at least 1 to 2 mo. In spite of appropriate oxygenation (median FI(O(2)) at 28 d = 0.32; range, 0.21 to 0.50) and ventilatory strategies to prevent volutrauma, the baboons exhibited pulmonary pathologic lesions known to occur in extremely immature humans of less than 1,000 g: alveolar hypoplasia, variable saccular wall fibrosis, and minimal, if any, airway disease. The CLD baboon lungs showed significantly decreased alveolization and internal surface area measurements when compared with term and term + 2-mo air-breathing controls. A decrease in capillary vasculature was evident by PECAM staining, accompanied by dysmorphic changes. Significant elevations of TNF-alpha, IL-6, IL-8 levels, but not of IL-1beta and IL-10, in tracheal aspirate fluids were present at various times during the period of ventilatory support, supporting a role for mediator-induced autoinflammation. IL-8 levels were elevated in necropsy lavages of animals with significant lung infection. This model demonstrates that impaired alveolization and capillary development occur in immature lungs, even in the absence of marked hyperoxia and high ventilation settings.

Gains and losses from dexamethasone for neonatal chronic lung disease

Chronic lung disease is a common outcome of neonatal intensive care, especially among infants born very much before term. Inflammation is important in the pathogenesis of chronic lung disease. Because of their anti-inflammatory properties, corticosteroids should have a favourable impact on the disease process. Yet, two multicentre trials 1 Collaborative Dexamethasone Trial GroupDexamethasone therapy in neonatal chronic lung disease: an international, placebo-controlled trial. Pediatrics. 1991; 88: 421-427 PubMed Google Scholar , 2 Shinwell ES Karplus M Zmora E et al. Failure of early postnatal dexamethasone to prevent chronic lung disease in infants with respiratory distress syndrome. Arch Dis Child. 1996; 74: F33-F37 Crossref Google Scholar did not show that corticosteroids conferred any long-term benefit. Possible explanations were either that the corticosteroids were given too late (after 3 weeks of age) 1 Collaborative Dexamethasone Trial GroupDexamethasone therapy in neonatal chronic lung disease: an international, placebo-controlled trial. Pediatrics. 1991; 88: 421-427 PubMed Google Scholar or that, when given “early” (within 14 days of birth), the course was too short (only 3 days). 2 Shinwell ES Karplus M Zmora E et al. Failure of early postnatal dexamethasone to prevent chronic lung disease in infants with respiratory distress syndrome. Arch Dis Child. 1996; 74: F33-F37 Crossref Google Scholar Other, smaller, trials 3 Rastogi A Akintorin SM Bez ML Morales P Pildes RS A controlled trial of dexamethasone to prevent bronchopulmonary dysplasia in surfactant treated infants. Pediatrics. 1996; 98: 204-210 PubMed Google Scholar , 4 Yeh TF Lin YY Hseih WS et al. Early postnatal dexamethasone therapy for the prevention of chronic lung disease in preterm infants with respiratory distress syndrome: a multicentre clinical trial. Pediatrics. 1997; 100: E3 Crossref PubMed Scopus (146) Google Scholar of early but longer courses of dexamethasone have shown a positive effect.

Chronic interstitial lung diseases in childhood: bronchopulmonary dysplasia and exogenous allergic alveolitis

Bronchopulmonary dysplasia (BPD) is a chronic lung disease that develops in preterm infants treated with oxygen and positive-pressure ventilation for respiratory distress syndrome. Despite the introduction of new treatment modalities (surfactant therapy, high-frequency oscillation) and improvements in the outcome of critically ill preterm infants, BPD has become an extremely important complication of neonatal intensive care and the most common form of chronic lung disease in infants. Specific pathogenesis, treatment modalities, prognosis, and multidisciplinary approaches to the prevention of BPD are described in detail. Extrinsic allergic alveolitis ("hypersensitivity pneumonitis") is a rare pulmonary disease in childhood due to inhaled organic dust, containing fungal antigens, thermophilic actinomycetes, or avian proteins. Diagnosis is often difficult, but it should be considered in every child with persistent and otherwise unexplained respiratory symptoms.

Bombesin-like peptide mediates lung injury in a baboon model of bronchopulmonary dysplasia.

The etiology of bronchopulmonary dysplasia (BPD), a chronic lung disease of infants surviving respiratory distress syndrome, remains fundamentally enigmatic. BPD is decreasing in severity but continues to be a major problem in pediatric medicine, being especially prevalent among very premature infants. Increased numbers of pulmonary neuroendocrine cells containing bombesin-like peptide (BLP) have been reported to occur in human infants with BPD. We tested the hypothesis that BLP mediates BPD using the hyperoxic baboon model. Urine BLP levels increased soon after birth only in 100% O2-treated 140-d animals which developed BPD, correlating closely with severity of subsequent chronic lung disease. Similar elevations in urine BLP were observed in the 125-d baboon "interrupted gestation" model of BPD. Postnatal administration of anti-BLP antibody attenuated clinical and pathological evidence of chronic lung disease in the hyperoxic baboon model. Urine BLP could be a biological predictor of infants at risk for BPD, and blocking BLP postnatally could be useful for BPD prevention.

Plasma 3-nitrotyrosine is elevated in premature infants who develop bronchopulmonary dysplasia.

Premature infants are susceptible to bronchopulmonary dysplasia (BPD), a chronic lung disease of infancy that appears to be caused in part by oxidative stress from hyperoxia. To investigate the possible role of nitric oxide-derived oxidants such as peroxynitrite in the etiology of BPD, we measured levels of plasma 3-nitrotyrosine, which is produced by the reaction of peroxynitrite with proteins. Ten premature infants who developed BPD, defined as requiring supplemental oxygen beyond 36 weeks' postmenstrual age, were identified retrospectively from a group of subjects enrolled in a clinical trial of antenatal therapy. Serial plasma samples had been collected on these infants during the first month of life as part of the trial. Sixteen comparison premature infants were identified from the same population: 5 had no lung disease, 6 had respiratory distress syndrome that resolved, and 5 had residual lung disease at 28 days of life that resolved by 36 weeks' postmenstrual age. Plasma 3-nitrotyrosine levels were measured using a solid phase immunoradiochemical method. All 3-nitrotyrosine values in infants without BPD were <0.25 ng/mg protein, and levels did not change with postnatal age. Plasma 3-nitrotyrosine concentrations were significantly higher in infants with BPD, increasing approximately fourfold during the first month of life. For the 20 infants who had blood samples available at 28 days of life, plasma 3-nitrotyrosine levels correlated with the fraction of inspired oxygen that the infant was receiving (r = 0.7). Plasma 3-nitrotyrosine content is increased during the first month of life in infants who develop BPD. This suggests that peroxynitrite-mediated oxidant stress may contribute to the development of this disease in premature infants and that 3-nitrotyrosine may be useful as an early plasma indicator of infants at risk for developing BPD.

Gastroesophageal reflux(GER) and Chronic lung disease(CLD) in Very low birthweight(VLBW) infants 1189

Gastroesophageal reflux(GER) may be associated withchronic lung disease(CLD) in very low birthweight infants. Esophageal pH monitoring is the gold standard for diagnosis of GER. Early diagnosis and antireflux therapy may lead to amelioration of CLD in infants with GER.

Echocardiographic evidence of aortopulmonary collaterals in premature infants after closure of ductus arteriosus.

Aortopulmonary collaterals occur in a variety of congenital heart diseases, in chronic pulmonary infection and abscesses, in association with lung tumors, and after multiple pulmonary emboli. In patients with congenital cyanotic heart disease aortopulmonary collaterals mainly occur in conditions with reduced pulmonary blood flow. We investigated 12 preterm low-birth-weight infants, gestational age 29.3+/-3.3 weeks, with respiratory failure who suffered from moderate to severe chronic lung disease after a period of mechanical ventilation. All patients developed aortopulmonary collaterals after closure of a patent ductus arteriosus. Aortopulmonary collaterals could be displayed clearly by color Doppler echocardiography and originated mainly from the descending aorta or the aortic arch. Hypoxic and hypercapnic episodes favored the development of aortopulmonary collaterals, which disappeared after pulmonary hemodynamics and respiratory function had improved. In only one patient coiling of a large col lateral vessel had to be performed. Systemic-to-pulmonary collateral vessels potentially aggravate chronic lung disease by increasing collateral pulmonary blood flow and reducing lung compliance. We conclude that aortopulmonary collaterals occur in bronchopulmonary dysplasia and can cause major problems in ventilated premature infants. Echocardiographic evaluation is important to prevent aggravation of chronic lung disease of infants at risk.

Chronic lung disease in infants--long-term pulmonary sequelae.

Chronic lung disease in infants--long-term pulmonary sequelae.

Advances and issues in bronchopulmonary dysplasia

Introduction Bronchopulmonary dysplasia (BPD) can truly be considered a disease of medical progress. It was first fully described in the literature and named by Northway et el.’ in 1967. Dr. Northway, a radiologist at Stanford University, recognized a distinctive radiographic pattern of chronic lung disease in infants surviving in the neonatal intensive care unit there directed by Dr. Philip Sunshine. More specifically, these patients were premature infants with respiratory distress syndrome (hyaline membrane disease) who were being managed with intermittent positivepressure ventilation using mechanical ventilators that delivered relatively high pressure and oxygen tension to the respiratory tract. Concurrently, one of the other pioneer neonatal intensive care units at Vanderbilt University observed the same phenomenon as Dr. Mildred Stallman’s team managed to increase the survival of premature infants with respiratory failure by using miniaturized mechanical ventilation instruments. Earlier in the decade, the death of Patrick Kennedy (son of President and Mrs. John Kennedy) focused the nation’s attention on the respiratory complications of premature birth. This tragic death and the combination of new knowledge and technology in newborn care led to the establishment of neonatal intensive care units and the emergence of new diseases such as BPD. It is ironic that a quarter of a century later, BPD remains an enigma to neonatologists and pediatric pulmonologists and intensivists. It is for this reason that several specialized centers of research supported by the National Institutes of Health have concentrated their efforts on enhancing and understanding the basic science and clinical aspects of lung injury, cellular repair processes, and treatment of BPD. Fortunately, during the past few years, there have been significant advances in our understanding of BPD. Although a number of issues remain, more progress is expected in the future as lung injury processes become explained. This review will summarize research developments of the past few years on the bases of published articles in refereed journals. More detailed information can be obtained in the scientific reports per se.