Contribution of pulmonary surfactant with inhaled nitric oxide for treatment of pulmonary hypertension

BACKGROUND: Combined therapy of inhaled nitric oxide (iNO) with pulmonary surfactant replacement was reported to improve oxygenation in patients or animal models of persistent pulmonary hypertension of the newborn with pulmonary surfactant deficiency lung. To evaluate the potential of iNO for the treatment of persistent pulmonary hypertension of the newborn, pulmonary arterial pressure (PAP) was measured during iNO before and after pulmonary surfactant replacement in an animal model of pulmonary hypertension with surfactant deficiency. METHODS: Seven newborn piglets were injected with L-nitro-arginine-methylester to produce an animal model of pulmonary hypertension. After PAP increased, iNO (30 p.p.m.) was introduced. Then iNO was stopped, and animals were subjected to lung lavage with saline. After recording the effect of iNO, all animals then received exogenous pulmonary surfactant installation. After surfactant treatment, iNO was again introduced. RESULTS: Pulmonary arterial pressure and systemic arterial pressure were increased significantly by >30% after infusion of L-nitro-arginine-methylester. During iNO only PAP was reduced significantly. Respiratory system compliance decreased significantly after lung lavage, and increased significantly after pulmonary surfactant replacement with concomitant increase of PaO2. In contrast, significant reduction of PAP with iNO before and after pulmonary surfactant replacement were also observed. The reduction ratios of PAP under each condition were 75.2 +/- 7.4%, 81.3 +/- 3.1%, and 79.1 +/- 5.3%, respectively (not significant among conditions). CONCLUSION: These results suggest that iNO is still a potent pulmonary arterial vasodilator even under pulmonary surfactant deficiency in an animal model of pulmonary hypertension.     

Pediatric postprimary pulmonary tuberculosis

BACKGROUND: Postprimary pulmonary tuberculosis (TB) is not commonly seen in children. OBJECTIVE: The purpose of this study was to determine the radiographic findings and patient characteristics of pediatric postprimary pulmonary TB. MATERIALS AND METHODS: We reviewed the clinical charts and chest radiographs in six patients. RESULTS: The radiographic findings of pediatric postprimary pulmonary TB include upper-lobe consolidation and cavitation, multifocal ill-defined airspace opacities, evidence of prior pulmonary TB, and apical pleural thickening. Pleural effusions and lymphadenopathy are not commonly present. Although postprimary disease typically does not affect young children, five of the children in this series were less than ten years of age at the time of presentation. CONCLUSION: The possibility of postprimary TB should be considered in pediatric patients at risk for this disease who present with upper-lobe pulmonary consolidation and cavitation. These patients are highly infectious and early recognition and treatment can limit transmission of TB.     

Ductal shunting, high pulmonary blood flow, and pulmonary hemorrhage

OBJECTIVE: To describe the relationship among ductal shunting, estimated pulmonary blood flow, and pulmonary hemorrhage in very preterm infants. STUDY DESIGN: A total of 126 babies born before 30 weeks' gestation (median gestation 27 weeks, range 23 to 29 weeks) underwent echocardiography at 5, 12, 24, and 48 hours of age; measurements included right and left ventricular output, superior vena cava flow, and color Doppler diameter of any ductal shunt. Pulmonary blood flow was derived from the sum of right ventricular output and estimated ductal shunt flow. RESULTS: Twelve (9.5%) babies had a pulmonary hemorrhage at a mean age of 38 hours. Compared with the rest of the cohort, these 12 babies were less likely to have had antenatal steroids (59% vs 90%) and were less mature (26 weeks vs 27 weeks). At the echocardiogram closest to the pulmonary hemorrhage, 11 (92%) of the 12 babies had a significant patent ductus arteriosus >1.6 mm in diameter (median 2 mm, range 0.7 to 2.4 mm), and the median pulmonary blood flow was 326 mL/kg/min (range 210 to 598 mL/kg/min). These measurements were significantly higher than those found in the rest of the cohort in the same period (median duct diameter 0.5 mm [range 0 to 2.9 mm], median pulmonary blood flow 237 mL/kg/min [range 107 to 569 mL/kg/min]). At 5-hour echocardiography the babies with pulmonary hemorrhage had significantly larger diameter ducts but similar pulmonary blood flow. CONCLUSIONS: Pulmonary hemorrhage in preterm babies is associated with significant ductal shunting and high estimated pulmonary blood flow.     

肺静脉指数对肺血减少型先天性心脏病肺血管发育的评估

目的 探索能更准确反映肺血管发育及肺血流情况的指标,为外科手术方案的选择提供依据.方法 采用74例肺血减少型先天性心脏病心血管造影序列,测量左右肺动脉及4根肺静脉直径,分别计算Nakata指数,McGoon指数,肺静脉指数(PVI),分别与术后情况进行相关分析.结果 左、右侧肺静脉大小分别与左右肺动脉大小高度相关,左侧肺静脉与左肺动脉远端的相关性为0.73,左侧肺静脉与左肺动脉近端的相关性为0.72,右侧肺静脉与右肺动脉远端的相关性为0.67,右侧肺静脉与右肺动脉近端的相关性为0.71.PVI与术后监护时间,呼吸机维持时间,正性肌力药物用量的相关性分别为-0.51,-0.478和-0.693,均比Nakata指数,McGoon指数明显增高,能更准确的反映整个肺血管的发育情况.右室流出道重建术后无低心排组与低心排组的McGoon指数分别为1.97±0.58与1.36±0.51(t=2.347,P＜0.05),两组Nakata指数分别为(269±124)mm2/m2和(164±106)mm2/m2(t=2.218,P＜0.05),PVI分别为(273±125)mm2/m2和(152±77)mm2/m2(t=2.936,P＜0.01),低心排组肺血管值均明显小于无低心排组.当PVI小于180 mm2/m2时,术后易出现血流动力学不稳定,低心排,甚至死亡.结论 肺动脉、肺静脉发育彼此相关,PVI能更准确反映肺血管发育及肺血流情况的形态学指标,为外科手术方案的选择提供有效依据.     

Laboratorial tests in pulmonary diseases

OBJECTIVE: The authors present a review about the diagnosis of pulmonary diseases, with special emphasis on laboratorial procedures. METHODS: The most important articles about laboratorial procedures were selected through Medline search. RESULTS: To diagnose pulmonary diseases we need to evaluate clinical history, laboratorial tests, several radiografic techniques, bronchoscopy, thoracentesis and lung biopsy among others. We present the main laboratorial tests which include the clinical tests and pulmonary function evaluation to diagnose these diseases. CONCLUSION: The laboratorial tests are part of pulmonary tests diagnosis. The obtained results should be associated with clinical history and the other diagnostic methods.     

The role of pulmonary resection in pulmonary interstitial emphysema in premature infants

The primary treatment of pulmonary interstitial emphysema is medical using ventilator manipulations, suctioning, positioning, and selective bronchial intubation. Three premature infants with pulmonary interstitial emphysema causing progressive hyperinflation of one or more lobes failed to respond to medical management and were ventilator-dependent until the hyperinflated lobe(s) were removed. While the role of surgery in treating pulmonary interstitial emphysema is limited, the results can be beneficial. Offprint requests to: G. Stringel     

Echocardiographic findings of pulmonary atresia or critical pulmonary stenosis and intact ventricular septum in utero

BACKGROUND: Neonates with right ventricular outflow obstruction and intact ventricular septum show serious hemodynamic problems, such as severe hypoxemia, congestive heart failure due to massive tricuspid regurgitation, respiratory distress related to huge pulmonary hypoplasia or ventricular dysfunction due to right ventricle-coronary communication. Recent advances in fetal diagnosis include many cases of in utero diagnosis of pulmonary atresia or critical pulmonary stenosis and intact ventricular septum. METHOD: Among the fetuses examined from April 1994 to March 1998, five fetuses were found with pulmonary atresia (PA) or critical pulmonary stenosis (CPS). Fetal echocardiograms were reviewed to elucidate the accuracy of fetal information and the efficacy of fetal diagnosis in the perinatal management of patient with CPS or PA and intact ventricular septum. RESULTS: The five cases were divided into two groups: two with a very small right ventricle (group 1) and three with a tripartite right ventricle (group 2). Fetal cardiomegaly and right atrial dilatation were prominent in group 2, whereas cardiac sizes were normal in group 1. Serial fetal examination in one group 2 fetus revealed developing right ventricular hypertrophy in utero. All group 2 cases showed massive tricuspid regurgitation (TR). Estimated right ventricular pressures from TR always exceeded the systemic blood pressures of gestational age-matched neonates. Reversed flow through the ductus arteriosus was recorded in both groups and ductus-dependent pulmonary circulation after birth was anticipated. Patency of both tricuspid and pulmonary valves was difficult to recognize in utero, as was right ventricle-coronary artery communication. Four of the five cases were maternally transported and survived palliative and/or definitive intervention. One fetus with chromosomal abnormality was observed without intervention during infancy and received palliative surgery when she was two years old. CONCLUSION: Fetal hemodynamic information was useful for making decisions not only after birth, but also in utero, and may eventually result in improving the prognosis of babies with PA/CPS. Serial observation of the fetuses with PA/CPS may also suggest the possible pathogenesis of PA/CPS in utero.     

The effects of obesity on pulmonary function

Methods: Sixty four obese patients underwent physical examination, standardised pulmonary function tests (spirometry, lung volumes, and single breath diffusion capacity for carbon monoxide), and DEXA scan measurements. The trunk and subtotal (total - head) body fat mass were used as surrogate index of body adiposity. Results: Sixteen girls and 48 boys with median age and body mass index (BMI) of 12 years (interquartile range (IQR): 10–14) and 30.1 kg/m² (IQR: 27.2–32.8) respectively were studied. None of the patients had clinical evidence of cardiopulmonary disease. Reduction in functional residual capacity (median FRC 93% predicted, IQR: 68.5–116.5%) and impairment of diffusion capacity (median DLco 83.5% predicted, IQR: 70.0–100.7%) were the most common abnormalities in our cohort, being observed in 30 (46%) and 21 (33%) patients respectively. Obstructive ventilatory impairment was found in three patients. There was significant negative correlation between the degree of reduction of FRC but not DLco with DEXA scan measurements, but such a relation was not found when BMI was used as the indicator of obesity. Conclusion: Reduction in FRC and diffusion impairment were the commonest abnormalities found in our cohort of obese patients. Reduction in static lung volume was correlated with the degree of obesity.     

The effects of obesity on pulmonary function.

AIMS: (1) To determine the predominant pulmonary function abnormality in our population of obese children; and (2) to assess the correlation between the severity of lung function impairment and the degree of obesity as assessed by dual energy x ray absorptiometry (DEXA). METHODS: Sixty four obese patients underwent physical examination, standardised pulmonary function tests (spirometry, lung volumes, and single breath diffusion capacity for carbon monoxide), and DEXA scan measurements. The trunk and subtotal (total - head) body fat mass were used as surrogate index of body adiposity. RESULTS: Sixteen girls and 48 boys with median age and body mass index (BMI) of 12 years (interquartile range (IQR): 10-14) and 30.1 kg/m2 (IQR: 27.2-32.8) respectively were studied. None of the patients had clinical evidence of cardiopulmonary disease. Reduction in functional residual capacity (median FRC 93% predicted, IQR: 68.5-116.5%) and impairment of diffusion capacity (median DLco 83.5% predicted, IQR: 70.0-100.7%) were the most common abnormalities in our cohort, being observed in 30 (46%) and 21 (33%) patients respectively. Obstructive ventilatory impairment was found in three patients. There was significant negative correlation between the degree of reduction of FRC but not DLco with DEXA scan measurements, but such a relation was not found when BMI was used as the indicator of obesity. CONCLUSION: Reduction in FRC and diffusion impairment were the commonest abnormalities found in our cohort of obese patients. Reduction in static lung volume was correlated with the degree of obesity.     

Massive pulmonary embolus without hypoxemia.

OBJECTIVE: To describe a patient who had been taking ibuprofen for 3 days before the diagnosis of a massive pulmonary embolus without hypoxemia. DESIGN: Institutional review board-approved case report. SETTING: Pediatric intensive care unit. PATIENT: A 16-yr-old male with a history of supraventricular tachycardia. RESULTS: The patient underwent an electrophysiology study and developed mild shortness of breath and then chest pain 2 and 4 days later, respectively. He took ibuprofen for 3 days. Evaluation 1 wk following the procedure revealed dyspnea and tachycardia. Arterial blood gas in room air was significant for hypocarbia without hypoxemia (Pao2, 108 mm Hg; Paco2, 28 mm Hg). Ventilation perfusion scan and computed axial tomography with intravenous contrast were consistent with a massive pulmonary embolus and left external iliac vein thrombus. He received anticoagulation, thrombolysis, a stent in the left iliac vein, and a filter in the inferior vena cava. Perfusion gradually improved and he was discharged home on oral anticoagulation. CONCLUSIONS: The absence of hypoxemia (including a normal alveolar-arterial oxygen difference) in our patient with a massive pulmonary embolus may have been related to cyclooxygenase inhibition due to ibuprofen, with improvement in ventilation-perfusion mismatch.     

Congenital pulmonary vein stenosis as a rare cause of pulmonary hypertension]

We report on the history, the diagnostic, and the operative procedure in an infant with congenital stenosis of all pulmonary veins. First symptoms such as failure to thrive, tachydyspnea, tachycardia and hepatomegaly occurred in the eighth week of life. Electrocardiography, 2-dimensional echocardiography and radiography of the chest were unspecific. After recurrent episodes of pulmonary oedema cardiac catheterization was performed: bilaterally elevated pulmonary artery wedge pressure and a normal left atrial pressure proved pulmonary venous obstruction. Severe stenosis of all pulmonary veins was apparent cineangiographically only by selective injections into the right and left pulmonary artery branches in wedge position. The operation (excision of the stenotic area and reimplantation using autologous pericardium) was unsuccessful as in most cases described in the literature. Congenital stenosis of all pulmonary veins is a rapidly progressive malformation. Death occurs usually in the first year of life with and without operation.     

Congenital pulmonary arteriovenous malformations

 We report the rare case of an 11-year-old boy who presented with intractable hypoxaemia and a pulmonary mass. Investigations revealed this to be a pulmonary arteriovenous malformation. It was entirely confined to the right middle lobe and was successfully treated via a right middle lobectomy. The relevant literature with respect to both diagnosis and treatment is reviewed. Accepted: 20 March 2000     

Longitudinal evaluation of pulmonary function tests in children with newborn screening for cystic fibrosis. Relationships with pulmonary infection. Study of 40 children undergoing 744 pulmonary function tests]

OBJECTIVES: To report longitudinal assessment of pulmonary function in children with neonatal screening for cystic fibrosis and its relationships with Pseudomonas aeruginosa (PA) chronic infection, nutritional status, sex, age and genotype. POPULATION AND METHODS: Children benefited systematically of 3 visits a year with pulmonary function tests (PFT) and bacteriological examination. Forty children and 744 PFTs were analysed, with 38 children during at least 4 years. RESULTS: We reported a decrease of pulmonary function tests with chronic PA infection and the genotype DeltaF508/DeltaF508. The decline was gradual and not different between not infected and recently infected children. The PFTs of children infected for a long times were very deteriorate, probably due to the fact that they were infected with multiresistant strains of PA. CONCLUSION: We think that it is important to survey pulmonary function before 5 years old in these early infected children. We should determinate if the important decrease of PFT in these early infected children is due to infection by PA mucoid.     

高肺血流性肺动脉高压大鼠肾上腺髓质素前体N端20肽的变化

目的：高肺血流性肺动脉高压的形成机制至今尚未完全阐明。该实验通过研究高肺血流性肺动脉高压大鼠肺组织肾上腺髓质素前体N端20肽( PAMP ) 表达以及血浆PAMP含量的变化,探讨PAMP在高肺血流性肺动脉高压形成中的作用。方法：16只雄性SD大鼠随机分为对照组和分流组,每组各8只。对分流组大鼠行腹主动脉-下腔静脉分流术。11周后,以右心导管法测定肺动脉收缩压（sPAP）、肺动脉舒张压（dPAP）和肺动脉平均压（mPAP）,观察肺动脉超微结构的变化。并且以放射免疫法测定血浆中PAMP含量,以免疫组织化学法检测肺组织中PAMP表达。结果：分流组大鼠sPAP、dPAP和mPAP均明显高于对照组（均P<0.01）。电镜下,肺腺泡内动脉内皮细胞增生、肿胀,内弹力层不规则,平滑肌细胞肥厚、向合成表型转化。并且分流组大鼠血浆PAMP含量明显高于对照组（P<0.01）,肺动脉内皮细胞和平滑肌细胞PAMP表达明显增强。结论：肺动脉和血浆PAMP表达的上调可能参与了高肺血流性肺动脉高压的形成。［中国当代儿科杂志,2007,9（6）：574-576］     

Idiopathic pulmonary hemosiderosis: case report

OBJECTIVE: To alert pediatricians about the possibillity of childhood Idiopathic Pulmonary Hemosiderosis, in cases of anemia associated with chronic lung disease. METHODS: This article documents a case of Idiopathic Pulmonary Hemosiderosis in a 6 year-old child, with histopathological documentation, and reviews it against published literature. RESULTS: A 6 year-old child with history of anemia and lung disease characterized by wheezing, recurrent pneumonia and digital clubbing was admitted to the hospital for investigation, where he suffered sudden respiratory failure and hemoptysis.He was submitted to a lung biopsy which showed a histopathological diagnosis compatible with pulmonary hemosiderosis. Therapy with high doses of corticosteroids was initiated with a good early response. After two and a half months of therapy he had a new bleeding episode, culminating in death. CONCLUSIONS: Idiopathic Pulmonary Hemosiderosis should be included as a possible diagnosis of children with anemia and chronic lung disease. This case is a good example.     

Aggressive manifestations of inflammatory pulmonary pseudotumor in children

We present three cases that illustrate the locally invasive radiographic appearance that inflammatory pulmonary pseudotumor can assume. Awareness and inclusion of inflammatory pseudotumor in the differential diagnosis of aggressive pleuropulmonary and mediastinal processes may have critical treatment implications. Received: 5 February 1998 Accepted: 29 June 1998     

Re-admissions to inpatient paediatric pulmonary rehabilitation

OBJECTIVE: To describe re-admission rates, identify reasons for re-admission and examine characteristics of children requiring re-admission to inpatient pulmonary rehabilitation. METHODOLOGY: Retrospective record review of infants and toddlers (less than three years of age) requiring oxygen or ventilator support discharged from an inpatient paediatric pulmonary rehabilitation programme between 1992 and 1999. RESULTS: Forty-one initial admissions resulted in 45 readmissions with a mean re-admission rate of 1.1 (SD = 1.41) re-admissions per child. Children with re-admissions (n = 22, 54%) required significantly more ventilator support (p = 0.001) and nursing care (p = 0.001) and were transferred to acute care more frequently (p = 0.002) than children without re-admissions. One-half of the children re-admitted to inpatient pulmonary rehabilitation were re-admitted two or more times. CONCLUSIONS: Based on this cohort of children, dependence on supplemental oxygen and/or mechanical ventilation and medical complexity may be indicators that children will require re-admission to rehabilitation following a transfer back to acute care. Further examination of re-admission rates and reasons and children's clinical characteristics may have predictive value and provide practice improvement opportunities.     

Gastrostomy in infants with neonatal pulmonary disease

OBJECTIVE: To report our experience of enteral feeding via gastrostomy in children with severe chronic neonatal lung disease, failure to thrive, and oral aversive behavior after initial hospitalization. POPULATION: Thirteen patients were studied. All children had chronic lung disease of neonatal onset and were severely malnourished. They received enteral nutrition via a gastrostomy at a median age of 13 months (range: 8-35). RESULTS: Z-scores for weight-for-height increased significantly, from -3.4 to -1.9 after four months of enteral nutrition. Caloric intake increased significantly from 100% to 140% of the recommended daily allowance for age. Pulmonary status remained stable for all patients and oxygenation was normal. There was an aggravation of oral aversive behavior in 7 of the 13 children, especially those children who were ventilated and hospitalized for a long time (median duration: 195 days). The median follow-up of patients after gastrostomy was 30 months (range: 8-54) and only six patients could be weaned from enteral nutrition. CONCLUSION: Enteral nutrition via gastrostomy is efficient, and provides the means to improve caloric intake and nutritional status. Gastrostomy is a safe and convenient technique that should be considered early in the course of treatment for infants presenting with malnutrition related to neonatal pulmonary disease.     

Treatment of persistent pulmonary hypertension of the newborn

OBJECTIVE: To review the medical literature, emphasizing the new scientific advances in the treatment of persistent pulmonary hypertension of the newborn. SOURCES: Literature review using Medline and Cochrane library. SUMMARY OF THE FINDINGS: Persistent pulmonary hypertension of the newborn (PPHN) is characterized by an increase in pulmonary vascular resistance associated with right to left shunt through the foramen ovale or ductus arteriosus, leading to marked hypoxemia and respiratory failure. The balance between the vasoconstrictor (endothelin) and vasodilator (nitric oxide and prostaglandin I2) mediators plays an important role in the regulation of the transition from fetal circulation with high pulmonary vascular resistance to postnatal circulation with low pulmonary vascular resistance. In addition to general management, cardiovascular support, the treatment of the cause of the PPHN, and the use of selective pulmonary vasodilator such as inhaled nitric oxide (iNO) are indicated. Furthermore, the combined therapy with iNO and high-frequency oscillatory ventilation significantly improved the oxygenation of patients who were refractory to iNO therapy and conventional ventilation. The practice of hyperventilation and the administration of nonspecific pulmonary vasodilators (tolazoline) should be avoided. On the other hand, the administration of surfactant to patients with PPHN due to meconium aspiration should be considered. However, if all these therapies fail, extracorporeal membrane oxygenation (ECMO) should be considered as rescue therapy. CONCLUSIONS: The mortality due to PPHN has significantly decreased with the use of new therapies, and the major concern today is the quality of life of these patients, especially in terms of neuropsychomotor development.     

Nasopharyngeal aspiration for diagnosis of pulmonary tuberculosis.

BACKGROUND: Confirmation of pulmonary tuberculosis (PTB) in young children is difficult as they seldom expectorate sputum. AIM: To compare sputa obtained by nasopharyngeal aspiration and by sputum induction for staining and culture of Mycobacterium tuberculosis. PATIENTS AND METHODS: Patients from Mulago Hospital, Kampala with symptoms suggestive of PTB were considered for inclusion in the study. Those with a positive tuberculin test and/or a chest radiograph compatible with tuberculosis were recruited. Infection with human immunodeficiency virus (HIV) was confirmed by duplicate enzyme-labelled immunosorbent assay or in children <15 months by polymerase chain reaction (PCR). Direct PCR was undertaken on 82 nasopharyngeal aspirates. RESULTS: Of 438 patients referred, 94 were recruited over a period of 5 months. Median (range) age was 48 (4-144) months. Of 63 patients tested, 69.8% were infected with HIV. Paired and uncontaminated culture results were available for 88 patients and smear results for 94 patients. Nasopharyngeal aspirates were smear-positive in 8.5% and culture-positive in 23.9%. Induced sputa were smear-positive in 9.6% and culture positive in 21.6%. Overall, 10.6% were smear-positive, 25.5% were culture-positive and 26.6% had smear and/or culture confirmed tuberculosis. Direct PCR on nasopharyngeal aspirates had a sensitivity of 62% and specificity of 98% for confirmation of culture-positive tuberculosis. CONCLUSIONS: Nasopharyngeal aspiration is a useful, safe and low-technology method for confirmation of PTB and, like sputum induction, can be undertaken in outpatient clinics.