Arnold C.G. Platzker

Childhood sequelae of infant lung disease: Exercise and pulmonary function abnormalities after bronchopulmonary dysplasia

To determine the long-term pulmonary sequelae and effect on exercise tolerance of bronchopulmonary dysplasia (BPD), we studied 10 children at a mean age of 10.4 years, who had been born prematurely, survived respiratory distress syndrome, and subsequently developed BPD, and compared them with eight age-matched normal children born at term. Pulmonary function tests and graded exercise stress tests were performed. Residual volume, the ratio between residual volume and total lung capacity, vital capacity, forced expiratory volume in 1 second, forced expiratory flow between 25% and 75% of vital capacity, and maximal expiratory flows at 80%, 70%, and 60% of total lung capacity were all abnormal (P less than 0.02) in the children with BPD, compared with control values. Pre-exercise transcutaneous CO2 tension was higher (P less than 0.05) in the BPD group than in the control group. At maximal workload, tcPCO2 remained high in patients with BPD compared with control values (P less than 0.05). Arterial oxygen saturation at maximal workload fell below pre-exercise levels in the BPD group (P less than 0.05) but not in control children. There were no differences in maximal oxygen consumption between the BPD group and control children. Exercise-induced bronchospasm occurred in 50% of the BPD group, but not in the control group. We conclude that long-term survivors of BPD have evidence of airway obstruction, hyperinflation, and airway hyperreactivity, compared with a control group. Aerobic fitness was not significantly different in the BPD and control groups, but was achieved in the BPD group at the expense of a fall in SaO2 and a rise in tcPCO2.

Furosemide acutely decreases airways resistance in chronic bronchopulmonary dysplasia

We studied the effects of furosemide on pulmonary mechanics in 10 infants with bronchopulmonary dysplasia aged 41 +/- 1 (SE) weeks post-conception, gestational age at birth 30 +/- 1 wk, birth weight 1370 +/- 200 gm. Thoracic gas volume, airways resistance, and specific airway conductance were measured in an infant body pressure plethysmograph during quiet breathing. Dynamic pulmonary compliance was measured using an esophageal balloon. Infants with BPD had greater Raw, lower SGaw, and lower Cdyn than did 16 normal control infants. Within one hour after administration of furosemide 1 mg/kg IV to infants with BPD, Raw fell 36 +/- 13%, SGaw increased 84 +/- 22%, and Cdyn increased 54 +/- 13%; TGV did not change. Diuretic treatment of BPD in infants is associated with rapid, short-term improvement in Raw and Cdyn.

Incidence of premature birth and neonatal respiratory disease in infants of HIV-positive mothers

OBJECTIVE We sought to determine the prematurity rate in infants of HIV-positive mothers and to characterize the incidence and severity of neonatal respiratory disease in this population. STUDY DESIGN From 1990 to 1994, 600 live-born infants of HIV-infected mothers were enrolled prenatally (73%) or postnatally (27%) from five U.S. centers. Logistic regression was used to determine the association of HIV status in the infant with prematurity (< or = 37 weeks), low birth weight (< or = 2.5 kg), and very low birth weight (< or = 1.5 kg) rates. The incidence of respiratory distress syndrome (RDS), bronchopulmonary dysplasia, meconium aspiration syndrome, and neonatal pneumonia was compared with anticipated rates for gestational age and birth weight. RESULTS Very high rates of prematurity (19%), low birth weight (18.3%), and very low birth weight (3.3%) were found in the infants of HIV-positive mothers; and HIV infection in the infant was associated with younger gestational age. The overall incidence of RDS was 3% (17/600), which coincided with the anticipated rate, after adjusting for prematurity and birth weight. Only five infants (all < or = 1.5 kg) had bronchopulmonary dysplasia, and none required assisted ventilation beyond 14 days. Three term infants had mild meconium aspiration syndrome, and there were no cases of documented neonatal pneumonia. CONCLUSION Infants born to HIV-positive mothers exhibited high prematurity and low birth weight rates, and the odds of prematurity were higher in infants who were infected with HIV. Despite the high incidence of prematurity and perinatal risk of this population, incidence and severity of neonatal respiratory disease were not higher than would be expected from available neonatal data in populations not exposed to HIV.

Long-term pulmonary sequelae of meconium aspiration syndrome

To determine the incidence of long-term sequelae after meconium aspiration syndrome (MAS), we studied 11 children who had MAS at age 8.2 +/- 0.2 years (mean +/- SD) and nine healthy control subjects with pulmonary function and exercise stress tests. The MAS children had evidence of mild airway obstruction, hyperinflation, and increased closing volumes in comparison with control values. During graded exercise stress tests on a treadmill, MAS children achieved normal maximal oxygen consumption and anaerobic threshold without a significant fall in arterial oxygen saturation or increase in CO2 tension. Exercise-induced bronchospasm occurred in four (36%) MAS subjects but in none of the control subjects. We conclude that children surviving MAS have long-term pulmonary sequelae, including airway obstruction, hyperinflation, elevated closing volumes, and airway hyperreactivity; yet they achieve normal aerobic capacity. These findings are similar, although less severe, than those after prematurity and bronchopulmonary dysplasia.

Long-term pulmonary sequelae in children who were treated with extracorporeal membrane oxygenation for neonatal respiratory failure.

Objective. Extracorporeal membrane oxygenation (ECMO) is a life-saving therapy for neonates with intractable respiratory failure, but the long-term pulmonary outcome is unknown. Our aim was to investigate the long-term pulmonary sequelae of these children. Study Design. We studied 50 children at 11.1 ± 1.1 years (mean ± SD) who had been treated with neonatal ECMO for meconium aspiration syndrome (38%), sepsis (18%), sepsis with pneumonia (12%), congenital diaphragmatic hernia (12%), congenital heart disease (8%), persistent pulmonary hypertension of the newborn (6%), and respiratory distress syndrome (4%) and 27 healthy controls (10.8 ± 1.6 years). All subjects completed a respiratory questionnaire and performed pulmonary function and graded cardiopulmonary exercise testing. Results. Neonatal ECMO survivors had hyperinflation (median residual volume: 131%), airway obstruction (median forced expired volume in 1 second: 79%), lower oxygen saturation with exercise, and lower peak oxygen consumption than controls. The ECMO group achieved similar exercise minute ventilation to controls, with more rapid and shallow breathing. ECMO survivors had an increased frequency of exercise-induced bronchospasm. Those who required higher inspired oxygen tension and ventilator pressures after weaning from ECMO had lower forced expired volume in 1 second and oxygen saturation values. Conclusion. Neonatal ECMO survivors experience lung injury lasting into later childhood. Lung dysfunction correlates with the extent and duration of barotrauma and oxygen exposure as neonates.

Developmental Pattern of Maximal Transdiaphragmatic Pressure in Infants during Crying

Summary: Diaphragm strength was measured as maximal transdiaphragmatic pressure (Pdi) during airway occlusion in 38 infants aged 11.6 ± 0.5 (S.E.) months postconception (mpc), range 8–21 mpc. All infants were asymptomatic at the time of study and required no mechanical ventilatory assistance. Ten infants had previous surgical correction of abdominal wall defects (gastroschisis/omphalocele); 10 infants had previous surgical correction of congenital diaphragmatic hernia; and 18 infants had no thoracic or abdominal surgery. The mean maximal Pdi for all infants was 72 ± 3 cmH2O. There were no significant differences between the three groups. All infants with a maximal Pdi of less than 60 cmH2O were aged less than 10 mpc. After 13 mpc there was no significant increase in maximal Pdi. Between the ages 8–13 mpc there was a significant positive correlation between maximal Pdi and age postconception (r = 0.87, P < 0.0005), reflecting a developmental pattern of increasing maximal transdiaphragmatic pressure in infants during crying.

Primary Hyperinsulinemia Reduces Surface Active Material Flux in Tracheal Fluid of Fetal Lambs

Summary: We sought to test the hypothesis that hyperinsulinemia per se alters the flux of surface active material (SAM) into tracheal fluid by continuously infusing insulin (0.24 ± 0.04 units/kg/hr, mean ± S.E.) from 112 through 135 days gestation into five chronically catheterised fetal lambs, from which tracheal fluid could be collected.Serum insulin levels in these fetuses (95 ± 10 μU/ml) were greater than in five chronically catheterised control fetuses of the same gestational age (10 ± 1 μU/ml, P < 0.001) and in the mothers (38 ± 6 μU/ml, P < 0.001). Serum glucose levels in the insulin-treated fetuses (10 ± 1 mg/dl) were lower than in the control fetuses (19 ± 1 mg/dl, P < 0.001) and in the mothers (60 ± 3 mg/dl, P < 0.001). Arterial blood gases (pH 7.37 ± 0.01, PO2 23.3 ± 0.05 mm Hg, PCO2 41.5 ± 0.9 mm Hg) and hematocrit (33 + 1% at 127 days gestation and 31 ± 1% at 135 days gestation) in the insulin treated fetuses were not different from the controls.SAM flux into the tracheal fluid of the insulin-treated fetuses was 1 μg/kg/hr, coefficient of variation 373%. This was lower than SAM flux in the control fetuses (26 μg/kg/hr, coefficient of variation 28%, P < 0.01). Moreover, among the control fetuses, SAM began to appear in tracheal fluid at 119 days gestation and was present in all five fetuses by 125 days gestation, whereas SAM did not begin to appear in the insulin-treated fetuses until 127 days gestation and did not appear at all in three of them.Speculation: Chronic hyperinsulinemia reduces surface active material flux into tracheal fluid of fetal lambs. This effect may be partially mediated by reduced substrate (glucose) availability for surface active material phospholipid synthesis, storage, and/or secretion.

Review of Intensive Care Unit Admissions for Asthma

A review of ICU admissions for asthma to the Childrens Hospital of Los Angeles was conducted for the period January 1969 through July 1977. The admission rate remained relatively constant during this period. Patients requiring ICU admission tended to be young, intractable severe asthmatics whose asthma started at a very young age. There were three patients who had no previous history of asthma. The incidence of pneumomitis/atelectasis was somewhat greater than has been reported for patients hospitalized for status asthmaticus. A significant number of children received neither intravenous corticosteroids, sympathomimetics nor oxygen therapy while hospitalized prior to transfer to the ICU. Those children receiving mechanical ventilation or intravenous isoproterenol tended to be somewhat younger and had a higher incidence of pneumonitis/atelectasis and more abnormal blood gas determina tions than their counterparts who were not similarly treated. Mechanical ventilation was administered to 15 patients and 19 patients received intra venous isoproterenol. Intravenous isoproterenol resulted in prompt improve ment in most patients; except for one patient who experienced cardiac arrhyth mia (reversed when the dosage was decreased), this medication was well-tolerated.

Interstitial pneumonitis and pleural effusion in a one-year-old child with an abdominal tumor

A l-YEar-, l-MONTH-OLD WHITE BOY was admitted to Childrens Hospital of Los Angeles because of respiratory distress. He had been well until 10 months of age, when a left upper quadrant mass was noted on routine physical examination. Radiologic studies at another hospital showed indentation of the greater curvature of the stomach, but results of intravenous pyelographic and abdominal sonographic studies were normal. The mass continued to enlarge, and he was referred to this hospital at 12 months of age. The past medical and family histories were unremarkable, growth and development had been normal, immunizations were current, and the review of systems was completely negative. Physical examination revealed a well-developed, wellnourished child in no distress who weighed 12.4 kg. Pulse rate was 94/minute, respirations 24/minute, temperature 37.6~ and blood pressure 100/62 mm Hg. Positive physical findings were confined to the abdomen, where there was a firm, irregular, nontender, fixed, 7 x 5 cm mass in the left upper quadrant. The mass extended beneath the costal margin, but seemed to be separate from the liver and spleen. There were no skin lesions or enlarged lymph nodes. The white blood cell count was 12,200/mm ~ with 53% neutrophils, 40% lymphocytes, 6% monocytes, and 1% eosinophils. The hemoglobin was 13.4 gm/dl, and platelets appeared normal in number and morphology on the blood smear. The SGOT was 56 IU/L (normal, 8 to 40 IU/L) and the SGPT was 54 IU/L

Cardiovascular responses to autonomic blockade in brain-injured fetal lambs.

The cardiovascular responses to autonomic blockade were investigated in 15 late-gestation fetal lambs in utero. 4 animals had normal brains and 11 had hydranencephalic-like cerebral injury secondary to bilateral carotid artery obstruction (BCO). Following atropine administration, heart rate increased only 0.7 +/- 0.7% in the BCO lambs compared to 25.7 +/- 5.2% in the controls. alpha-Blockade with phentolamine resulted in a small decrease in systolic (2.2 +/- 0.8%) and diastolic (1.8 +/- 1.4%) blood pressure, and beta-blockade with propranolol produced a small decrease in heart rate (2.5 +/- 0.8%) as compared to control fetuses. Post mortem examination revealed extensive destruction of the cerebrum but normal hypothalamus and brain stem. These data suggest that supramedullary modification of autonomic cardiovascular control involves the cerebrum.